Materiały źródłowe

• #1 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  Molecular pathways in colorectal carcinogenesis involve several complex genetic and epigenetic modulations that cause normal colonic mucosa to metamorphose into a benign polyp and subsequently into a malignant tumor. […] In 2015, the molecular classification for colorectal cancers was unified into one system with four distinct groups, also called as consensus molecular subtypes. This led to an enhanced understanding of molecular and immune signatures which has implications on predicting the clinical behavior as well as response to different therapeutic agents. […] Pathogenesis of CRC is multi-phasic, starting from the earliest dysplastic lesion called aberrant crypt focus to adenomatous polyp to invasive cancer. On the molecular level, Vogelstein and colleagues proposed that development of carcinogenesis depends on progressive accumulation of changes beneficial to tumor growth over time leading eventually to an invasive malignancy. This is called the adenoma-carcinoma sequence.

• #2 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis of CRC is a testament to the dysregulation of these signaling cascades, which culminates in the malignant transformation of colonic epithelium. […] At the core of CRC’s pathogenesis lie aberrant signaling pathways that drive tumorigenesis, sustain cancer cell proliferation, and enable metastatic dissemination. These pathways, which include the Wnt/-catenin, RAS/RAF/MEK/ERK, phosphoinositide 3-kinase (PI3K)/AKT, and transforming growth factor-beta (TGF-) circuits, among others, are often dysregulated by a confluence of genetic mutations, such as adenomatous polyposis coli (APC), kirsten rat sarcoma viral oncogene homolog (KRAS), and PIK3CA.

• #3 Colorectal cancer carcinogenesis: a review of mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4850121/

  Colorectal cancer (CRC) arises from one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. […] Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. […] Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. […] CRCs can arise from one or a combination of three different mechanisms, namely chromosomal instability (CIN), CpG island methylator phenotype (CIMP), and microsatellite instability (MSI). […] The classical CIN pathway begins with the acquisition of mutations in the adenomatous polyposis coli (APC), followed by the mutational activation of oncogene KRAS and the inactivation of the tumor suppressor gene, TP53.

• #4 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  Molecular pathways in colorectal carcinogenesis involve several complex genetic and epigenetic modulations that cause normal colonic mucosa to metamorphose into a benign polyp and subsequently into a malignant tumor. […] In 2015, the molecular classification for colorectal cancers was unified into one system with four distinct groups, also called as consensus molecular subtypes. This led to an enhanced understanding of molecular and immune signatures which has implications on predicting the clinical behavior as well as response to different therapeutic agents. […] Pathogenesis of CRC is multi-phasic, starting from the earliest dysplastic lesion called aberrant crypt focus to adenomatous polyp to invasive cancer. On the molecular level, Vogelstein and colleagues proposed that development of carcinogenesis depends on progressive accumulation of changes beneficial to tumor growth over time leading eventually to an invasive malignancy. This is called the adenoma-carcinoma sequence.

• #5 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Mismatch repair (MMR) deficient tumours are characterized by a relatively high number of poly-nucleotide tandem repeats. This is caused by a deficiency in MMR proteins which are typically caused by epigenetic silencing and or inherited mutations (e.g., Lynch syndrome). 15 to 18 percent of colorectal cancer tumours have MMR deficiencies, with 3 percent developing due to Lynch syndrome. The role of the mismatch repair system is to protect the integrity of the genetic material within cells (i.e., error detecting and correcting). Consequently, a deficiency in MMR proteins may lead to an inability to detect and repair genetic damage, allowing for further cancer-causing mutations to occur and colorectal cancer to progress. […] The polyp to cancer progression sequence is the classical model of colorectal cancer pathogenesis. In this adenoma-carcinoma sequence, normal epithelial cells progress to dysplastic cells such as adenomas, and then to carcinoma, by a process of progressive genetic mutation. Central to the polyp to CRC sequence are gene mutations, epigenetic alterations, and local inflammatory changes. The polyp to CRC sequence can be used as an underlying framework to illustrate how specific molecular changes lead to various cancer subtypes.

• #6

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  Bowel cancer is a multifactorial disease arising from a combination of genetic predisposition and environmental factors. […] In this review, we summarised the origin of bowel cancer and the mechanism of its metastasis. […] The adenoma-carcinoma sequence was reported in 1980, elucidating the metamorphosis of normal colorectal epithelium to adenoma, and then to invasive and metastatic tumours. […] The accumulation of acquired genetic and epigenetic alterations that turn normal glandular epithelial cells into invasive adenocarcinomas is a critical element of bowel cancer development. […] The polyp-to-cancer progression sequence, also known as the adenoma-carcinoma sequence, was postulated in Vogelstein and Fearons pioneering and classic tumour development model. […] It connects genetic alterations to the order in which tumour morphology alters at different stages of cancer development, beginning with a step that promotes the formation of benign neoplasms (e.g. adenomas and sessile serrated polyps), then a step that promotes the progression to more histologically advanced neoplasms, and finally a step that transforms the tumours to invasive carcinoma.

• #7 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Colorectal-Cancer-Pathogenesis.aspx

  Colorectal cancer development begins with the formation of a small fixed adenoma. This progresses into a more advanced, larger fixed adenoma. The tumor further develops into a large carcinoma covering a wide circumference of the colon/rectum. More aggressive forms will grow even bigger and begin to block the lumen of the colon/rectum. […] The development of colorectal cancer is mainly due to genomic and epigenomic instability. Understanding more about its development will improve the diagnostics and treatment of colorectal cancer in the future. […] Both genetic and environmental factors are important in the development of colorectal cancer. […] The hereditary forms of colorectal cancer such as Lynch syndrome are caused by a mutation in one of the DNA mismatch repair genes, which include MLH1, MSH2, MSH6, PMS2, and EPCAM. Mutations in these genes inhibit the ability for proper mismatch repair during replication, causing an accumulation of DNA mutations. This can lead to microsatellite instability.

• #8

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  The pathway of CpG island methylator phenotype is described by the global hypermethylation of promoter CpG island sites, which also results in the inactivation of tumour suppressor genes. […] However, these pathways do not occur in isolation but overlap to some extent. […] In the conceptualisation of these pathways, although there are still some uncertainties in the molecular mechanisms underlying the development of colorectal tumours from early lesions to advanced ones, most bowel cancers develop slowly from adenomatous polyps or flat adenomas. […] Cancer metastasis is the process whereby primary tumour cells spread from the original tumour site and establish secondary tumour colonies in distant organs. […] The most common site of metastasis from bowel cancer is the liver, and this is often the only site where metastasis is observed.

• #9 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  This represents an alternative pathway to the evolution of colorectal cancer and phenotypically present as heterogenous outgrowths such as hyperplastic polyps, sessile serrated adenomas or mixed hyperplastic polyps/serrated adenoma. […] Mutations in colon cancer can be traced to two modes of genomic instability: chromosomal instability (CIN) and microsatellite instability. Chromosomal instability can be observed in about 70% of CRC cases. […] According to the classical adenoma to carcinoma model, mutation in Apc gene instigates progression to carcinoma via chromosomal instability, which involves various numerical chromosomal aberrations, most commonly chromosome 18, sub chromosomal aberrations, and loss of heterozygosity. […] A subgroup of sporadic colorectal tumors is typified by microsatellite instability and V600 mutant BRAF. The pathogenetic hallmark is epigenetic silencing of mismatch repair proteins mediated via CpG sequence hypermethylation.

• #10 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  The development of sporadic colon cancer is thought to be influenced by diet, lifestyle, environmental factors, and acquired somatic mutations. […] It is well established that sporadic CRC is a genetic disease caused by sequential accumulation of mutations in multiple genes. […] Over the past three decades, molecular genetic studies have identified several crucial gene defects that underlie predisposition to sporadic CRC. […] The majority of sporadic CRCs are due to events that result from aberrations in the CIN pathway. […] The CIN pathway is an adenoma-carcinoma sequence model which suggests that a stepwise pattern of mutational activation of oncogenes and inactivation of tumor suppressor genes result in CRC. […] Among the earliest events in sporadic CRC progression pathway is the loss of the APC gene. Genetic disruption of the APC gene or its inactivation by hypermethylation of the APC promoter leads to Wnt/-catenin signaling activation.

• #11 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  This represents an alternative pathway to the evolution of colorectal cancer and phenotypically present as heterogenous outgrowths such as hyperplastic polyps, sessile serrated adenomas or mixed hyperplastic polyps/serrated adenoma. […] Mutations in colon cancer can be traced to two modes of genomic instability: chromosomal instability (CIN) and microsatellite instability. Chromosomal instability can be observed in about 70% of CRC cases. […] According to the classical adenoma to carcinoma model, mutation in Apc gene instigates progression to carcinoma via chromosomal instability, which involves various numerical chromosomal aberrations, most commonly chromosome 18, sub chromosomal aberrations, and loss of heterozygosity. […] A subgroup of sporadic colorectal tumors is typified by microsatellite instability and V600 mutant BRAF. The pathogenetic hallmark is epigenetic silencing of mismatch repair proteins mediated via CpG sequence hypermethylation.

• #12 Colorectal cancer carcinogenesis: a review of mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4850121/

  The CIMP pathway is characterized by promoter hypermethylation of various tumor suppressor genes, most importantly MGMT and MLH1. […] The MSI pathway involves the inactivation of genetic alterations in short repeated sequences. […] Disruptions in the DNA damage pathway and excess telomere breakage can lead to chromosomal instability. […] The damaged DNA is repaired by four mechanisms, namely base excision repair (BER), double-stranded break repair (DSBR), mismatch repair (MMR), and nucleotide excision repair (NER). […] The tumor suppressor transcription factor 53 (TP53) is located on chromosome 17, which is activated under stress. […] The hypermethylation of the MLH1 promoter in MSI-H sporadic CRCs is found in 83%-100% of tumors. […] Hypermethylation is noted in seven gene promoters in the normal to adenoma transition, and in four of these seven genes from adenoma to carcinoma. […] The aberrations in chromatin-remodeling genes, such as ATP-dependent chromatin remodelers, chromodomain helicase 7 (CHD7) and CHD8, may also be associated with CIMP tumors.

• #13 Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

  https://www.mdpi.com/1422-0067/22/1/130

  The APC gene inhibits transition from the G0/G1 to the S phase of the cell cycle. […] In this regard, it is well known that β-catenin is the main controller of the Wnt signaling pathway. […] The wild-type APC protein negatively controls the Wnt signaling by regulating the ubiquitin-mediated proteasomal breakdown of the transcription factor β-catenin. […] Disruption of the APC protein results in enhanced Wnt signaling by intracellular β-catenin stabilization, which stimulates transcription of Wnt targeted genes and enhances TCF targets with increase in cell growth, differentiation, spread, and adhesion of colorectal cells. […] The TP53 gene, located on the short arm of chromosome 17, is known as the “guardian of the genome” and encodes proteins regulating cell cycle, DNA repair, senescence, and apoptosis.

• #14

  https://www.alliedacademies.org/articles/pathogenesis-of-colorectal-cancer-17691.html

  Colorectal malignant growth jest chorobą, która zaczyna się od komórek nabłonkowych wyściełających jelito grube lub odbytnicę, najczęściej z powodu zmian w szlaku sygnalizacyjnym Wnt, które zwiększają aktywność sygnalizacyjną. […] Najczęściej zmienionym genem w całym raku jelita grubego jest gen APC, który koduje białko APC. Białko APC zapobiega gromadzeniu się białka β-kateniny. Bez APC, β-katenina gromadzi się do znacznych poziomów i (przenosi się) do jądra, wiąże się z DNA i aktywuje transkrypcję protoonkogenów. […] Poza defektami w szlaku sygnalizacyjnym Wnt, muszą wystąpić inne zmiany, aby komórka stała się złośliwa. Białko p53, produkowane przez gen TP53, zazwyczaj monitoruje podział komórkowy i inicjuje ich zaprogramowaną śmierć, jeśli mają wady w szlaku Wnt. […] Czasami gen kodujący p53 nie jest zmieniony, ale inny białko ochronne, nazwane BAX, jest zmieniane zamiast tego.

• #15 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of genetic mutations in the Wnt signaling pathway that increases signaling activity. The Wnt signaling pathway normally plays an important role for normal function of these cells including maintaining this lining. Mutations can be inherited or acquired, and most probably occur in the intestinal crypt stem cell. The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein prevents the accumulation of -catenin protein. Without APC, -catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of proto-oncogenes. These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they can cause cancer. While APC is mutated in most colon cancers, some cancers have increased -catenin because of mutations in -catenin (CTNNB1) that block its breakdown, or have mutations in other genes with function similar to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.

• #16 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Colorectal-Cancer-Pathogenesis.aspx

  Genomic and epigenomic instability contributes greatly to the formation of colorectal cancers. […] Chromosomal instability is the presence of aneuploid or polyploid DNA. […] Colorectal cancers that have microsatellite instability account for ~15% of colorectal cancers. The mutations seen in this type of colorectal cancer are distinct from those seen in CIN colorectal cancers. […] Hypermethylation of gene loci containing CpG islands, as well as global DNA hypomethylation, can cause colorectal cancer. […] A global decrease in methylation has been identified in many colorectal cancers. The mechanisms responsible for this are unknown. […] The development of colorectal cancers is very complex, with many different causes.

• #17 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  The importance of Wnt/-catenin signaling in the genesis of CRC is further reflected in many CRCs (50%) with intact APC genes but high frequency of activating mutations in -catenin that harbors functionally significant phosphorylation sites. […] Another important genetic pathway contributing to CIN is KRAS. The KRAS gene belongs to the RAS family of oncogenes and is mutated in 30-50% of CRCs. […] Studies have also demonstrated the loss of tumor suppressor TP53 gene and 18q LOH as major contributors to the CIN phenotype. […] In addition to CIN pathway, about 10-15% of sporadic CRC are due to the MSI pathway. MSI is the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR). […] The proteins involved in MMR form a complex that binds to the mismatch, identifies the correct strand of DNA, then subsequently excises the error and repairs the mismatch.

• #18 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  The importance of Wnt/-catenin signaling in the genesis of CRC is further reflected in many CRCs (50%) with intact APC genes but high frequency of activating mutations in -catenin that harbors functionally significant phosphorylation sites. […] Another important genetic pathway contributing to CIN is KRAS. The KRAS gene belongs to the RAS family of oncogenes and is mutated in 30-50% of CRCs. […] Studies have also demonstrated the loss of tumor suppressor TP53 gene and 18q LOH as major contributors to the CIN phenotype. […] In addition to CIN pathway, about 10-15% of sporadic CRC are due to the MSI pathway. MSI is the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR). […] The proteins involved in MMR form a complex that binds to the mismatch, identifies the correct strand of DNA, then subsequently excises the error and repairs the mismatch.

• #19 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  Cells with abnormally functioning MMR tend to accumulate mutations (insertions or deletions) in microsatellites located in DNA coding regions, generating frameshift mutations and subsequently leading to sporadic CRCs. […] The Serrated pathway initiated CRCs are highlighted by the presence of BRAF mutation and epigenetic silencing of genes that are involved in cell differentiation, DNA repair, and cell-cycle control, but not APC. […] Point mutation in BRAF (V600E) causes constitutive activation of this kinase as well as its insensitivity to negative feedback mechanisms, leading to enhanced MAPK/ERK signaling. […] The progression of sporadic CRCs through the Serrated pathway is accelerated by p16 inactivation through promoter hypermethylation. […] It is possible that no two CRCs are alike and only a few mutations are common to most sporadic CRCs. Therefore, each tumor has its own unique combination of genetic alterations. […] These different pathways will undoubtedly interact with each other, and may even modify these routes to carcinogenesis.

• #20 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Mismatch repair (MMR) deficient tumours are characterized by a relatively high number of poly-nucleotide tandem repeats. This is caused by a deficiency in MMR proteins which are typically caused by epigenetic silencing and or inherited mutations (e.g., Lynch syndrome). 15 to 18 percent of colorectal cancer tumours have MMR deficiencies, with 3 percent developing due to Lynch syndrome. The role of the mismatch repair system is to protect the integrity of the genetic material within cells (i.e., error detecting and correcting). Consequently, a deficiency in MMR proteins may lead to an inability to detect and repair genetic damage, allowing for further cancer-causing mutations to occur and colorectal cancer to progress. […] The polyp to cancer progression sequence is the classical model of colorectal cancer pathogenesis. In this adenoma-carcinoma sequence, normal epithelial cells progress to dysplastic cells such as adenomas, and then to carcinoma, by a process of progressive genetic mutation. Central to the polyp to CRC sequence are gene mutations, epigenetic alterations, and local inflammatory changes. The polyp to CRC sequence can be used as an underlying framework to illustrate how specific molecular changes lead to various cancer subtypes.

• #21 Colorectal cancer carcinogenesis: a review of mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4850121/

  The CIMP pathway is characterized by promoter hypermethylation of various tumor suppressor genes, most importantly MGMT and MLH1. […] The MSI pathway involves the inactivation of genetic alterations in short repeated sequences. […] Disruptions in the DNA damage pathway and excess telomere breakage can lead to chromosomal instability. […] The damaged DNA is repaired by four mechanisms, namely base excision repair (BER), double-stranded break repair (DSBR), mismatch repair (MMR), and nucleotide excision repair (NER). […] The tumor suppressor transcription factor 53 (TP53) is located on chromosome 17, which is activated under stress. […] The hypermethylation of the MLH1 promoter in MSI-H sporadic CRCs is found in 83%-100% of tumors. […] Hypermethylation is noted in seven gene promoters in the normal to adenoma transition, and in four of these seven genes from adenoma to carcinoma. […] The aberrations in chromatin-remodeling genes, such as ATP-dependent chromatin remodelers, chromodomain helicase 7 (CHD7) and CHD8, may also be associated with CIMP tumors.

• #22 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Mismatch repair (MMR) deficient tumours are characterized by a relatively high number of poly-nucleotide tandem repeats. This is caused by a deficiency in MMR proteins which are typically caused by epigenetic silencing and or inherited mutations (e.g., Lynch syndrome). 15 to 18 percent of colorectal cancer tumours have MMR deficiencies, with 3 percent developing due to Lynch syndrome. The role of the mismatch repair system is to protect the integrity of the genetic material within cells (i.e., error detecting and correcting). Consequently, a deficiency in MMR proteins may lead to an inability to detect and repair genetic damage, allowing for further cancer-causing mutations to occur and colorectal cancer to progress. […] The polyp to cancer progression sequence is the classical model of colorectal cancer pathogenesis. In this adenoma-carcinoma sequence, normal epithelial cells progress to dysplastic cells such as adenomas, and then to carcinoma, by a process of progressive genetic mutation. Central to the polyp to CRC sequence are gene mutations, epigenetic alterations, and local inflammatory changes. The polyp to CRC sequence can be used as an underlying framework to illustrate how specific molecular changes lead to various cancer subtypes.

• #23 Colorectal cancer carcinogenesis: a review of mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4850121/

  The CIMP pathway is characterized by promoter hypermethylation of various tumor suppressor genes, most importantly MGMT and MLH1. […] The MSI pathway involves the inactivation of genetic alterations in short repeated sequences. […] Disruptions in the DNA damage pathway and excess telomere breakage can lead to chromosomal instability. […] The damaged DNA is repaired by four mechanisms, namely base excision repair (BER), double-stranded break repair (DSBR), mismatch repair (MMR), and nucleotide excision repair (NER). […] The tumor suppressor transcription factor 53 (TP53) is located on chromosome 17, which is activated under stress. […] The hypermethylation of the MLH1 promoter in MSI-H sporadic CRCs is found in 83%-100% of tumors. […] Hypermethylation is noted in seven gene promoters in the normal to adenoma transition, and in four of these seven genes from adenoma to carcinoma. […] The aberrations in chromatin-remodeling genes, such as ATP-dependent chromatin remodelers, chromodomain helicase 7 (CHD7) and CHD8, may also be associated with CIMP tumors.

• #24 Colorectal cancer carcinogenesis: a review of mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4850121/

  The CIMP pathway is characterized by promoter hypermethylation of various tumor suppressor genes, most importantly MGMT and MLH1. […] The MSI pathway involves the inactivation of genetic alterations in short repeated sequences. […] Disruptions in the DNA damage pathway and excess telomere breakage can lead to chromosomal instability. […] The damaged DNA is repaired by four mechanisms, namely base excision repair (BER), double-stranded break repair (DSBR), mismatch repair (MMR), and nucleotide excision repair (NER). […] The tumor suppressor transcription factor 53 (TP53) is located on chromosome 17, which is activated under stress. […] The hypermethylation of the MLH1 promoter in MSI-H sporadic CRCs is found in 83%-100% of tumors. […] Hypermethylation is noted in seven gene promoters in the normal to adenoma transition, and in four of these seven genes from adenoma to carcinoma. […] The aberrations in chromatin-remodeling genes, such as ATP-dependent chromatin remodelers, chromodomain helicase 7 (CHD7) and CHD8, may also be associated with CIMP tumors.

• #25 Colorectal cancer carcinogenesis: a review of mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4850121/

  The CIMP pathway is characterized by promoter hypermethylation of various tumor suppressor genes, most importantly MGMT and MLH1. […] The MSI pathway involves the inactivation of genetic alterations in short repeated sequences. […] Disruptions in the DNA damage pathway and excess telomere breakage can lead to chromosomal instability. […] The damaged DNA is repaired by four mechanisms, namely base excision repair (BER), double-stranded break repair (DSBR), mismatch repair (MMR), and nucleotide excision repair (NER). […] The tumor suppressor transcription factor 53 (TP53) is located on chromosome 17, which is activated under stress. […] The hypermethylation of the MLH1 promoter in MSI-H sporadic CRCs is found in 83%-100% of tumors. […] Hypermethylation is noted in seven gene promoters in the normal to adenoma transition, and in four of these seven genes from adenoma to carcinoma. […] The aberrations in chromatin-remodeling genes, such as ATP-dependent chromatin remodelers, chromodomain helicase 7 (CHD7) and CHD8, may also be associated with CIMP tumors.

• #26 Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

  https://www.mdpi.com/1422-0067/22/1/130

  DNA methylation is the addition of a methyl group to cytosine in the 5′-position that is catalyzed by DNA methyltransferases via covalent linkage within a CG dinucleotide sequence within the promoter region, termed CpG transcription. […] In normal cells, the majority of the CpG sites are heavily methylated while CpG islands, usually located in the promoter regions of genes, are unmethylated. […] However, following cancer initiation, hypermethylation within the promoter region may lead to inactivation of tumor-suppressor genes, while global hypomethylation is associated with genomic instability and chromosomal aberrations. […] Many genes are identified to be methylated and silenced in CRC, some commonly methylated ones include APC, MLH1, MGMT, SFRP1, SFRP2, CDKN2A, TIMP3, VIM, SEPT, CDH1 and HLTF. […] CIMP tumors significantly correlated with age, female sex, proximal colon location, as well as MSI, KRAS and BRAF mutations. […] The molecular pathways involved in the pathogenesis of CRC are depicted in Figure 2.

• #27 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  This represents an alternative pathway to the evolution of colorectal cancer and phenotypically present as heterogenous outgrowths such as hyperplastic polyps, sessile serrated adenomas or mixed hyperplastic polyps/serrated adenoma. […] Mutations in colon cancer can be traced to two modes of genomic instability: chromosomal instability (CIN) and microsatellite instability. Chromosomal instability can be observed in about 70% of CRC cases. […] According to the classical adenoma to carcinoma model, mutation in Apc gene instigates progression to carcinoma via chromosomal instability, which involves various numerical chromosomal aberrations, most commonly chromosome 18, sub chromosomal aberrations, and loss of heterozygosity. […] A subgroup of sporadic colorectal tumors is typified by microsatellite instability and V600 mutant BRAF. The pathogenetic hallmark is epigenetic silencing of mismatch repair proteins mediated via CpG sequence hypermethylation.

• #28 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  This represents an alternative pathway to the evolution of colorectal cancer and phenotypically present as heterogenous outgrowths such as hyperplastic polyps, sessile serrated adenomas or mixed hyperplastic polyps/serrated adenoma. […] Mutations in colon cancer can be traced to two modes of genomic instability: chromosomal instability (CIN) and microsatellite instability. Chromosomal instability can be observed in about 70% of CRC cases. […] According to the classical adenoma to carcinoma model, mutation in Apc gene instigates progression to carcinoma via chromosomal instability, which involves various numerical chromosomal aberrations, most commonly chromosome 18, sub chromosomal aberrations, and loss of heterozygosity. […] A subgroup of sporadic colorectal tumors is typified by microsatellite instability and V600 mutant BRAF. The pathogenetic hallmark is epigenetic silencing of mismatch repair proteins mediated via CpG sequence hypermethylation.

• #29 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  Cells with abnormally functioning MMR tend to accumulate mutations (insertions or deletions) in microsatellites located in DNA coding regions, generating frameshift mutations and subsequently leading to sporadic CRCs. […] The Serrated pathway initiated CRCs are highlighted by the presence of BRAF mutation and epigenetic silencing of genes that are involved in cell differentiation, DNA repair, and cell-cycle control, but not APC. […] Point mutation in BRAF (V600E) causes constitutive activation of this kinase as well as its insensitivity to negative feedback mechanisms, leading to enhanced MAPK/ERK signaling. […] The progression of sporadic CRCs through the Serrated pathway is accelerated by p16 inactivation through promoter hypermethylation. […] It is possible that no two CRCs are alike and only a few mutations are common to most sporadic CRCs. Therefore, each tumor has its own unique combination of genetic alterations. […] These different pathways will undoubtedly interact with each other, and may even modify these routes to carcinogenesis.

• #30 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  Cells with abnormally functioning MMR tend to accumulate mutations (insertions or deletions) in microsatellites located in DNA coding regions, generating frameshift mutations and subsequently leading to sporadic CRCs. […] The Serrated pathway initiated CRCs are highlighted by the presence of BRAF mutation and epigenetic silencing of genes that are involved in cell differentiation, DNA repair, and cell-cycle control, but not APC. […] Point mutation in BRAF (V600E) causes constitutive activation of this kinase as well as its insensitivity to negative feedback mechanisms, leading to enhanced MAPK/ERK signaling. […] The progression of sporadic CRCs through the Serrated pathway is accelerated by p16 inactivation through promoter hypermethylation. […] It is possible that no two CRCs are alike and only a few mutations are common to most sporadic CRCs. Therefore, each tumor has its own unique combination of genetic alterations. […] These different pathways will undoubtedly interact with each other, and may even modify these routes to carcinogenesis.

• #31 Wnt signaling in colorectal cancer: pathogenic role and therapeutic target | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01616-7

  The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. […] As a functional effector molecule of Wnt signaling, the modification and degradation of -catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). […] The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis.

• #32 Wnt signaling in colorectal cancer: pathogenic role and therapeutic target | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01616-7

  Most colorectal cancers are caused by mutations that activate the Wnt/-catenin pathway. […] The Wnt/-catenin pathway plays a central role in the carcinogenesis and maintenance of colorectal cancer (CRC). […] The prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence and subsequent metastatic spread, which are maintained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling. […] The Wnt/-catenin signaling pathway is one of the main regulators of homeostasis and cancer stemness, and germ cell tumors, as the malignant tumor type closest to normal embryonic development, can be used as a unique model for studying the role of stem cells in tumors. […] The Wnt/-catenin signaling pathway and its components play an important role in the proliferation of dry and skin CSC.

• #33 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of genetic mutations in the Wnt signaling pathway that increases signaling activity. The Wnt signaling pathway normally plays an important role for normal function of these cells including maintaining this lining. Mutations can be inherited or acquired, and most probably occur in the intestinal crypt stem cell. The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein prevents the accumulation of -catenin protein. Without APC, -catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of proto-oncogenes. These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they can cause cancer. While APC is mutated in most colon cancers, some cancers have increased -catenin because of mutations in -catenin (CTNNB1) that block its breakdown, or have mutations in other genes with function similar to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.

• #34 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of genetic mutations in the Wnt signaling pathway that increases signaling activity. The Wnt signaling pathway normally plays an important role for normal function of these cells including maintaining this lining. Mutations can be inherited or acquired, and most probably occur in the intestinal crypt stem cell. The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein prevents the accumulation of -catenin protein. Without APC, -catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of proto-oncogenes. These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they can cause cancer. While APC is mutated in most colon cancers, some cancers have increased -catenin because of mutations in -catenin (CTNNB1) that block its breakdown, or have mutations in other genes with function similar to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.

• #35 Wnt signaling in colorectal cancer: pathogenic role and therapeutic target | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01616-7

  The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. […] As a functional effector molecule of Wnt signaling, the modification and degradation of -catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). […] The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis.

• #36 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of genetic mutations in the Wnt signaling pathway that increases signaling activity. The Wnt signaling pathway normally plays an important role for normal function of these cells including maintaining this lining. Mutations can be inherited or acquired, and most probably occur in the intestinal crypt stem cell. The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein prevents the accumulation of -catenin protein. Without APC, -catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of proto-oncogenes. These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they can cause cancer. While APC is mutated in most colon cancers, some cancers have increased -catenin because of mutations in -catenin (CTNNB1) that block its breakdown, or have mutations in other genes with function similar to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.

• #37 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  These pathways do not operate in isolation but are part of a complex and interwoven network of signaling events. Crosstalk between pathways can further complicate the cellular response and the development of effective therapeutic strategies. Understanding these interrelationships is crucial for the development of multi-targeted approaches in the treatment of CRC, which may improve the efficacy of existing therapies and contribute to the discovery of novel therapeutic agents. […] Enhanced Wnt signaling is a key driver of CRC development and progression. […] The Wnt pathway bifurcates into canonical and non-canonical branches, each with distinct cellular mechanisms and roles. […] The PI3K/Akt signaling axis exhibits pronounced activation in CRC, presenting a strategic target for interventions aimed at achieving clinical remission.

• #38 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  CRC is driven by the dysregulation of several key signaling pathways that collectively contribute to the hallmark capabilities acquired during tumorigenesis. In addition to the frequently implicated Wnt/-catenin signaling axis, the MAPK/ERK pathway emerges as a pivotal route for signal transduction that influences cellular proliferation and differentiation. […] The PI3K/AKT/mTOR cascade is another central signaling network that, when aberrant, leads to enhanced cellular growth, survival, and metabolism, thus providing a proliferative advantage to cancer cells. […] The TGF- pathway, with its multifaceted roles in cell growth and differentiation, exhibits a context-dependent function in CRC. It serves as a tumor suppressor in early neoplastic events but can pivotally switch to promote epithelial-to-mesenchymal transition (EMT) and metastasis in later stages of the disease.

• #39 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  These pathways do not operate in isolation but are part of a complex and interwoven network of signaling events. Crosstalk between pathways can further complicate the cellular response and the development of effective therapeutic strategies. Understanding these interrelationships is crucial for the development of multi-targeted approaches in the treatment of CRC, which may improve the efficacy of existing therapies and contribute to the discovery of novel therapeutic agents. […] Enhanced Wnt signaling is a key driver of CRC development and progression. […] The Wnt pathway bifurcates into canonical and non-canonical branches, each with distinct cellular mechanisms and roles. […] The PI3K/Akt signaling axis exhibits pronounced activation in CRC, presenting a strategic target for interventions aimed at achieving clinical remission.

• #40 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  The relationship between this pathway and glucose metabolism in CRC is particularly noteworthy. […] The oncogenic potential of PI3K/Akt extends to the phosphorylation of MDM2 at Ser186, which in turn mediates the ubiquitination and degradation of the tumor suppressor p53, a pivotal factor in the cellular response to genotoxic stress, thus promoting cell survival over apoptosis. […] The interaction between Fas and its ligand activates the caspase cascade through the Fas-associated death domain, leading to apoptosis. […] Crosstalk between Wnt signaling and other pathways is also a critical aspect of CRC pathogenesis. […] The dysregulation of the Ras/Raf/MEK/MAPK/ERK signaling pathway is a critical factor that drives the progression of CRC. […] In the context of CRC, somatic mutations within the MAPK pathway typically serve as activators for carcinogenesis.

• #41 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Approximately 70% of all human genes are expressed in colorectal cancer, with just over 1% having increased expression in colorectal cancer compared to other forms of cancer. Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated. […] Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF- signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer.

• #42 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  Gain of function mutations in oncogenes leads to constitutive activation and uncontrolled growth leading to cancer. Several oncogenes have been incriminated in colorectal tumorigenesis. […] According to the adenoma-carcinoma sequence model, as mentioned above, CRC origin is initiated by mutations in the Apc gene. […] TP53 is also known as the gatekeeper of the genome and is a pivotal mutation in a multitude of cancers including colon cancer. […] Mutations in the Phosphatase and Tensin homolog (PTEN) gene are linked with CRC in the young (50 years). […] TGF is a signaling molecule that regulates inhibition of cellular proliferation and induction of apoptosis. […] Over the years, there has been convincing evidence that right and left sided malignancies behave as two clinically disparate entities.

• #43 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  The relationship between this pathway and glucose metabolism in CRC is particularly noteworthy. […] The oncogenic potential of PI3K/Akt extends to the phosphorylation of MDM2 at Ser186, which in turn mediates the ubiquitination and degradation of the tumor suppressor p53, a pivotal factor in the cellular response to genotoxic stress, thus promoting cell survival over apoptosis. […] The interaction between Fas and its ligand activates the caspase cascade through the Fas-associated death domain, leading to apoptosis. […] Crosstalk between Wnt signaling and other pathways is also a critical aspect of CRC pathogenesis. […] The dysregulation of the Ras/Raf/MEK/MAPK/ERK signaling pathway is a critical factor that drives the progression of CRC. […] In the context of CRC, somatic mutations within the MAPK pathway typically serve as activators for carcinogenesis.

• #44 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  The relationship between this pathway and glucose metabolism in CRC is particularly noteworthy. […] The oncogenic potential of PI3K/Akt extends to the phosphorylation of MDM2 at Ser186, which in turn mediates the ubiquitination and degradation of the tumor suppressor p53, a pivotal factor in the cellular response to genotoxic stress, thus promoting cell survival over apoptosis. […] The interaction between Fas and its ligand activates the caspase cascade through the Fas-associated death domain, leading to apoptosis. […] Crosstalk between Wnt signaling and other pathways is also a critical aspect of CRC pathogenesis. […] The dysregulation of the Ras/Raf/MEK/MAPK/ERK signaling pathway is a critical factor that drives the progression of CRC. […] In the context of CRC, somatic mutations within the MAPK pathway typically serve as activators for carcinogenesis.

• #45 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Approximately 70% of all human genes are expressed in colorectal cancer, with just over 1% having increased expression in colorectal cancer compared to other forms of cancer. Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated. […] Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF- signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer.

• #46 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Approximately 70% of all human genes are expressed in colorectal cancer, with just over 1% having increased expression in colorectal cancer compared to other forms of cancer. Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated. […] Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF- signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer.

• #47 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  The importance of Wnt/-catenin signaling in the genesis of CRC is further reflected in many CRCs (50%) with intact APC genes but high frequency of activating mutations in -catenin that harbors functionally significant phosphorylation sites. […] Another important genetic pathway contributing to CIN is KRAS. The KRAS gene belongs to the RAS family of oncogenes and is mutated in 30-50% of CRCs. […] Studies have also demonstrated the loss of tumor suppressor TP53 gene and 18q LOH as major contributors to the CIN phenotype. […] In addition to CIN pathway, about 10-15% of sporadic CRC are due to the MSI pathway. MSI is the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR). […] The proteins involved in MMR form a complex that binds to the mismatch, identifies the correct strand of DNA, then subsequently excises the error and repairs the mismatch.

• #48 Colon cancer combined with obesity indicates improved survival- research on relevant mechanism | Aging

  https://www.aging-us.com/article/103972/text

  Obesity contributes to the incidence of various tumors, including colon cancer. […] We confirmed obesity as an independent prognostic factor for improved overall survival of colon cancer patients. […] We demonstrated that hypoxia pathways were repressed in obese patients by regulating miR-210. […] Immune checkpoints PD-1 and LAG3 were also downregulated in obese patients, which indicated enhanced immune surveillance. […] The frequency of PIK3CA and KRAS mutations was decreased in obese patients. […] In conclusion, our research demonstrated the potential mechanisms of prolonged survival in colon cancer patients combined with obesity, which may provide potential value for improving the prognosis of colon cancer. […] The prognosis of colon cancer patients is not satisfactory and survival is poor.

• #49 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  Gain of function mutations in oncogenes leads to constitutive activation and uncontrolled growth leading to cancer. Several oncogenes have been incriminated in colorectal tumorigenesis. […] According to the adenoma-carcinoma sequence model, as mentioned above, CRC origin is initiated by mutations in the Apc gene. […] TP53 is also known as the gatekeeper of the genome and is a pivotal mutation in a multitude of cancers including colon cancer. […] Mutations in the Phosphatase and Tensin homolog (PTEN) gene are linked with CRC in the young (50 years). […] TGF is a signaling molecule that regulates inhibition of cellular proliferation and induction of apoptosis. […] Over the years, there has been convincing evidence that right and left sided malignancies behave as two clinically disparate entities.

• #50 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  CRC is driven by the dysregulation of several key signaling pathways that collectively contribute to the hallmark capabilities acquired during tumorigenesis. In addition to the frequently implicated Wnt/-catenin signaling axis, the MAPK/ERK pathway emerges as a pivotal route for signal transduction that influences cellular proliferation and differentiation. […] The PI3K/AKT/mTOR cascade is another central signaling network that, when aberrant, leads to enhanced cellular growth, survival, and metabolism, thus providing a proliferative advantage to cancer cells. […] The TGF- pathway, with its multifaceted roles in cell growth and differentiation, exhibits a context-dependent function in CRC. It serves as a tumor suppressor in early neoplastic events but can pivotally switch to promote epithelial-to-mesenchymal transition (EMT) and metastasis in later stages of the disease.

• #51 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Beyond the defects in the Wnt signaling pathway, other mutations must occur for the cell to become cancerous. The p53 protein, produced by the TP53 gene, normally monitors cell division and induces their programmed death if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from a benign epithelial tumor into an invasive epithelial cell cancer. Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is mutated instead. […] Other proteins responsible for programmed cell death that are commonly deactivated in colorectal cancers are TGF- and DCC (Deleted in Colorectal Cancer). TGF- has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF- is not deactivated, but a downstream protein named SMAD is deactivated.

• #52 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  Gain of function mutations in oncogenes leads to constitutive activation and uncontrolled growth leading to cancer. Several oncogenes have been incriminated in colorectal tumorigenesis. […] According to the adenoma-carcinoma sequence model, as mentioned above, CRC origin is initiated by mutations in the Apc gene. […] TP53 is also known as the gatekeeper of the genome and is a pivotal mutation in a multitude of cancers including colon cancer. […] Mutations in the Phosphatase and Tensin homolog (PTEN) gene are linked with CRC in the young (50 years). […] TGF is a signaling molecule that regulates inhibition of cellular proliferation and induction of apoptosis. […] Over the years, there has been convincing evidence that right and left sided malignancies behave as two clinically disparate entities.

• #53 Colorectal cancer carcinogenesis: a review of mechanisms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4850121/

  The CIMP pathway is characterized by promoter hypermethylation of various tumor suppressor genes, most importantly MGMT and MLH1. […] The MSI pathway involves the inactivation of genetic alterations in short repeated sequences. […] Disruptions in the DNA damage pathway and excess telomere breakage can lead to chromosomal instability. […] The damaged DNA is repaired by four mechanisms, namely base excision repair (BER), double-stranded break repair (DSBR), mismatch repair (MMR), and nucleotide excision repair (NER). […] The tumor suppressor transcription factor 53 (TP53) is located on chromosome 17, which is activated under stress. […] The hypermethylation of the MLH1 promoter in MSI-H sporadic CRCs is found in 83%-100% of tumors. […] Hypermethylation is noted in seven gene promoters in the normal to adenoma transition, and in four of these seven genes from adenoma to carcinoma. […] The aberrations in chromatin-remodeling genes, such as ATP-dependent chromatin remodelers, chromodomain helicase 7 (CHD7) and CHD8, may also be associated with CIMP tumors.

• #54 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Beyond the defects in the Wnt signaling pathway, other mutations must occur for the cell to become cancerous. The p53 protein, produced by the TP53 gene, normally monitors cell division and induces their programmed death if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from a benign epithelial tumor into an invasive epithelial cell cancer. Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is mutated instead. […] Other proteins responsible for programmed cell death that are commonly deactivated in colorectal cancers are TGF- and DCC (Deleted in Colorectal Cancer). TGF- has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF- is not deactivated, but a downstream protein named SMAD is deactivated.

• #55 Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

  https://www.mdpi.com/1422-0067/22/1/130

  TP53 mutations or loss of function are reported in 50–75% of CRC cases; loss of p53-mediated pathways of apoptosis is an important determinant of progression from adenoma to malignant tumor. […] Loss of heterozygosity (LOH) refers to the absence of one of the two copies or alleles of a gene, with the remaining allele frequently being affected by mutation. […] LOH in the 18q region is most commonly observed in advanced CRC, accounting for approximately 70% of the cases, and is associated with poor prognosis in CRC. […] Another type of genomic instability in CRC is microsatellite instability (MSI), a distinctive characteristic of cancerous cells. […] MSI is the hallmark of HNPCC or Lynch syndrome and occurs in >95% of HNPCC cases. […] However, in the majority of sporadic CRCs, the underlying mechanism for CIN remains nascent and MSI comprises merely 15–20% of all CRC cases.

• #56 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Beyond the defects in the Wnt signaling pathway, other mutations must occur for the cell to become cancerous. The p53 protein, produced by the TP53 gene, normally monitors cell division and induces their programmed death if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from a benign epithelial tumor into an invasive epithelial cell cancer. Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is mutated instead. […] Other proteins responsible for programmed cell death that are commonly deactivated in colorectal cancers are TGF- and DCC (Deleted in Colorectal Cancer). TGF- has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF- is not deactivated, but a downstream protein named SMAD is deactivated.

• #57 CNIO researchers discover a molecular mechanism that initiates colon cancer – Biotech Spain

  https://biotech-spain.com/en/articles/cnio-researchers-discover-a-molecular-mechanism-that-initiates-colon-cancer/

  Colorectal colon or rectal cancer is the third most diagnosed type of cancer worldwide. […] A recent study published in Nature Communications describes a new molecular mechanism involved in the formation of colorectal tumours, which favours their progression towards more aggressive forms. […] In research with mouse models, the authors observed that a protein, called p53, began to degrade to decrease its presence in the early stages of tumour formation. This led to the emergence and development of cancer. […] The finding that p53 degradation initiates the tumour process in colon cancer is completely new. […] This study has found that the shortage of p53 favours tumour formation due to uncontrolled cell proliferation and also makes it easier for tumour cells to accumulate other mutations which jointly drive progression to more aggressive tumours.

• #58 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Field defects are important in the progression of colon cancer. The term „field cancerization” was first used in 1953 to describe an area or „field” of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards the development of cancer. Since then, the terms „field cancerization”, „field carcinogenesis”, „field defect”, and „field effect” have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. […] Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. Epigenetic alterations, distinct from mutations, change the protein expression of genes without changing the DNA sequence. One frequent type of epigenetic alteration in colorectal cancers is changed expression levels of particular microRNAs. microRNAs (miRNAs) are small RNAs that bind the 3 untranslated regions of their target messenger RNAs and cause suppression of protein translation. Down-regulation or up-regulation of microRNAs are epigenetic alterations since their altered regulation of messenger RNAs does not directly involve changing the DNA sequence. microRNAs are important epigenetic factors in colorectal cancer, with 164 microRNAs significantly altered in colorectal cancers. miRNAs have an average of 300 target genes per miRNA. About 60% of human protein-coding genes appear to be under the epigenetic control of miRNAs. As an example, miRNA-143 is downregulated in 88% of colorectal colon cancers and down-regulation of miRNA-143 causes up-regulation of protein expression of its target oncogene KRAS as well as its target DNA methylating protein DNMT3A.

• #59 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Field defects are important in the progression of colon cancer. The term „field cancerization” was first used in 1953 to describe an area or „field” of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards the development of cancer. Since then, the terms „field cancerization”, „field carcinogenesis”, „field defect”, and „field effect” have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. […] Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. Epigenetic alterations, distinct from mutations, change the protein expression of genes without changing the DNA sequence. One frequent type of epigenetic alteration in colorectal cancers is changed expression levels of particular microRNAs. microRNAs (miRNAs) are small RNAs that bind the 3 untranslated regions of their target messenger RNAs and cause suppression of protein translation. Down-regulation or up-regulation of microRNAs are epigenetic alterations since their altered regulation of messenger RNAs does not directly involve changing the DNA sequence. microRNAs are important epigenetic factors in colorectal cancer, with 164 microRNAs significantly altered in colorectal cancers. miRNAs have an average of 300 target genes per miRNA. About 60% of human protein-coding genes appear to be under the epigenetic control of miRNAs. As an example, miRNA-143 is downregulated in 88% of colorectal colon cancers and down-regulation of miRNA-143 causes up-regulation of protein expression of its target oncogene KRAS as well as its target DNA methylating protein DNMT3A.

• #60 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Field defects are important in the progression of colon cancer. The term „field cancerization” was first used in 1953 to describe an area or „field” of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards the development of cancer. Since then, the terms „field cancerization”, „field carcinogenesis”, „field defect”, and „field effect” have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. […] Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. Epigenetic alterations, distinct from mutations, change the protein expression of genes without changing the DNA sequence. One frequent type of epigenetic alteration in colorectal cancers is changed expression levels of particular microRNAs. microRNAs (miRNAs) are small RNAs that bind the 3 untranslated regions of their target messenger RNAs and cause suppression of protein translation. Down-regulation or up-regulation of microRNAs are epigenetic alterations since their altered regulation of messenger RNAs does not directly involve changing the DNA sequence. microRNAs are important epigenetic factors in colorectal cancer, with 164 microRNAs significantly altered in colorectal cancers. miRNAs have an average of 300 target genes per miRNA. About 60% of human protein-coding genes appear to be under the epigenetic control of miRNAs. As an example, miRNA-143 is downregulated in 88% of colorectal colon cancers and down-regulation of miRNA-143 causes up-regulation of protein expression of its target oncogene KRAS as well as its target DNA methylating protein DNMT3A.

• #61 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Field defects are important in the progression of colon cancer. The term „field cancerization” was first used in 1953 to describe an area or „field” of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards the development of cancer. Since then, the terms „field cancerization”, „field carcinogenesis”, „field defect”, and „field effect” have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. […] Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. Epigenetic alterations, distinct from mutations, change the protein expression of genes without changing the DNA sequence. One frequent type of epigenetic alteration in colorectal cancers is changed expression levels of particular microRNAs. microRNAs (miRNAs) are small RNAs that bind the 3 untranslated regions of their target messenger RNAs and cause suppression of protein translation. Down-regulation or up-regulation of microRNAs are epigenetic alterations since their altered regulation of messenger RNAs does not directly involve changing the DNA sequence. microRNAs are important epigenetic factors in colorectal cancer, with 164 microRNAs significantly altered in colorectal cancers. miRNAs have an average of 300 target genes per miRNA. About 60% of human protein-coding genes appear to be under the epigenetic control of miRNAs. As an example, miRNA-143 is downregulated in 88% of colorectal colon cancers and down-regulation of miRNA-143 causes up-regulation of protein expression of its target oncogene KRAS as well as its target DNA methylating protein DNMT3A.

• #62 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Field defects are important in the progression of colon cancer. The term „field cancerization” was first used in 1953 to describe an area or „field” of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards the development of cancer. Since then, the terms „field cancerization”, „field carcinogenesis”, „field defect”, and „field effect” have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. […] Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. Epigenetic alterations, distinct from mutations, change the protein expression of genes without changing the DNA sequence. One frequent type of epigenetic alteration in colorectal cancers is changed expression levels of particular microRNAs. microRNAs (miRNAs) are small RNAs that bind the 3 untranslated regions of their target messenger RNAs and cause suppression of protein translation. Down-regulation or up-regulation of microRNAs are epigenetic alterations since their altered regulation of messenger RNAs does not directly involve changing the DNA sequence. microRNAs are important epigenetic factors in colorectal cancer, with 164 microRNAs significantly altered in colorectal cancers. miRNAs have an average of 300 target genes per miRNA. About 60% of human protein-coding genes appear to be under the epigenetic control of miRNAs. As an example, miRNA-143 is downregulated in 88% of colorectal colon cancers and down-regulation of miRNA-143 causes up-regulation of protein expression of its target oncogene KRAS as well as its target DNA methylating protein DNMT3A.

• #63 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Epigenetic reductions of DNA repair enzyme expression may likely lead to the genomic and epigenomic instability characteristic of cancer. As summarized in the articles Carcinogenesis and Neoplasm, for sporadic cancers in general, a deficiency in DNA repair is occasionally due to a mutation in a DNA repair gene, but is much more frequently due to epigenetic alterations that reduce or silence expression of DNA repair genes. […] Epigenetic alterations involved in the development of colorectal cancer may affect a person’s response to chemotherapy.

• #64 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  The association between persistent inflammation and the emergence of neoplastic conditions is a well-established paradigm in cancer biology. […] Chronic inflammatory states, whether elicited by infectious agents, immune dysregulation, or environmental insults, are known to significantly elevate the risk of neoplastic transformation. […] In CRC specifically, conditions such as entrenched inflammatory bowel disease (IBD) and sustained gastrointestinal inflammation, often exacerbated by dietary patterns emblematic of a western diet, stand out as primary risk factors. […] Tumorigenesis necessitates two pivotal events: an initiating event characterized by an accumulation of genetic or epigenetic alterations leading to the suppression of tumor suppressor genes or the activation of oncogenes, and a promotion event involving the clonal expansion of cells harboring such mutations, culminating in the development of an overt tumor.

• #65 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  The association between persistent inflammation and the emergence of neoplastic conditions is a well-established paradigm in cancer biology. […] Chronic inflammatory states, whether elicited by infectious agents, immune dysregulation, or environmental insults, are known to significantly elevate the risk of neoplastic transformation. […] In CRC specifically, conditions such as entrenched inflammatory bowel disease (IBD) and sustained gastrointestinal inflammation, often exacerbated by dietary patterns emblematic of a western diet, stand out as primary risk factors. […] Tumorigenesis necessitates two pivotal events: an initiating event characterized by an accumulation of genetic or epigenetic alterations leading to the suppression of tumor suppressor genes or the activation of oncogenes, and a promotion event involving the clonal expansion of cells harboring such mutations, culminating in the development of an overt tumor.

• #66 Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-024-01953-7

  The association between persistent inflammation and the emergence of neoplastic conditions is a well-established paradigm in cancer biology. […] Chronic inflammatory states, whether elicited by infectious agents, immune dysregulation, or environmental insults, are known to significantly elevate the risk of neoplastic transformation. […] In CRC specifically, conditions such as entrenched inflammatory bowel disease (IBD) and sustained gastrointestinal inflammation, often exacerbated by dietary patterns emblematic of a western diet, stand out as primary risk factors. […] Tumorigenesis necessitates two pivotal events: an initiating event characterized by an accumulation of genetic or epigenetic alterations leading to the suppression of tumor suppressor genes or the activation of oncogenes, and a promotion event involving the clonal expansion of cells harboring such mutations, culminating in the development of an overt tumor.

• #67 Colorectal Cancer Pathogenesis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/15017

  A link between insulin resistance (IR), hyperinsulinemia and cancer, and changes in the expression of insulin receptors and insulin growth factor (IGF) system, including IGF-I, IGF-II, has been observed. […] Therefore, an IGF-I serum level within the upper part of the normal range has been associated with an increased risk of cancer development. […] The lipid peroxidation process leads to 4-hydroxynonenal (4-HNE) formation, an active compound that upregulates prostaglandin E2, which is directly correlated with an increased risk of CRC development. […] During cancer development, TNF-α is involved in cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis. […] Another important risk factor for CRC may be considered the gut microbiota disruption. […] Dysbiosis or imbalance of gut microbiota may cause chronic inflammation, which is recognized as one of the prime causes of CRC. […] Patients diagnosed with long-standing ulcerative colitis and Crohn’s disease have an elevated risk of developing CRC.

• #68 Colorectal Cancer Pathogenesis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/15017

  A link between insulin resistance (IR), hyperinsulinemia and cancer, and changes in the expression of insulin receptors and insulin growth factor (IGF) system, including IGF-I, IGF-II, has been observed. […] Therefore, an IGF-I serum level within the upper part of the normal range has been associated with an increased risk of cancer development. […] The lipid peroxidation process leads to 4-hydroxynonenal (4-HNE) formation, an active compound that upregulates prostaglandin E2, which is directly correlated with an increased risk of CRC development. […] During cancer development, TNF-α is involved in cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis. […] Another important risk factor for CRC may be considered the gut microbiota disruption. […] Dysbiosis or imbalance of gut microbiota may cause chronic inflammation, which is recognized as one of the prime causes of CRC. […] Patients diagnosed with long-standing ulcerative colitis and Crohn’s disease have an elevated risk of developing CRC.

• #69 The inflammatory pathogenesis of colorectal cancer | Nature Reviews Immunology

  https://www.nature.com/articles/s41577-021-00534-x

  The mutational landscape of colorectal cancer (CRC) does not enable predictions to be made about the survival of patients or their response to therapy. […] thus making CRC a prototypical example of the importance of an inflammatory microenvironment for tumorigenesis. […] Here, we review our current understanding of how colon cancer cells interact with their microenvironment, comprised of immune cells, stromal cells and the intestinal microbiome, to suppress or escape immune responses and how inflammatory processes shape the immune pathogenesis of CRC. […] This study shows the link between activation of WNT signalling, intestinal barrier defects and the induction of inflammation. […] This study demonstrates the link between intestinal inflammation and the expansion of microbial populations with genotoxic properties. […] This paper reports that bacteria can induce the same DNA mutation profile ex vivo as that found in patients with CRC. […] References 150 and 151 highlight the importance of fungi for the development of CRC.

• #70 The inflammatory pathogenesis of colorectal cancer | Nature Reviews Immunology

  https://www.nature.com/articles/s41577-021-00534-x

  The mutational landscape of colorectal cancer (CRC) does not enable predictions to be made about the survival of patients or their response to therapy. […] thus making CRC a prototypical example of the importance of an inflammatory microenvironment for tumorigenesis. […] Here, we review our current understanding of how colon cancer cells interact with their microenvironment, comprised of immune cells, stromal cells and the intestinal microbiome, to suppress or escape immune responses and how inflammatory processes shape the immune pathogenesis of CRC. […] This study shows the link between activation of WNT signalling, intestinal barrier defects and the induction of inflammation. […] This study demonstrates the link between intestinal inflammation and the expansion of microbial populations with genotoxic properties. […] This paper reports that bacteria can induce the same DNA mutation profile ex vivo as that found in patients with CRC. […] References 150 and 151 highlight the importance of fungi for the development of CRC.

• #71 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Field defects are important in the progression of colon cancer. The term „field cancerization” was first used in 1953 to describe an area or „field” of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards the development of cancer. Since then, the terms „field cancerization”, „field carcinogenesis”, „field defect”, and „field effect” have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. […] Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. Epigenetic alterations, distinct from mutations, change the protein expression of genes without changing the DNA sequence. One frequent type of epigenetic alteration in colorectal cancers is changed expression levels of particular microRNAs. microRNAs (miRNAs) are small RNAs that bind the 3 untranslated regions of their target messenger RNAs and cause suppression of protein translation. Down-regulation or up-regulation of microRNAs are epigenetic alterations since their altered regulation of messenger RNAs does not directly involve changing the DNA sequence. microRNAs are important epigenetic factors in colorectal cancer, with 164 microRNAs significantly altered in colorectal cancers. miRNAs have an average of 300 target genes per miRNA. About 60% of human protein-coding genes appear to be under the epigenetic control of miRNAs. As an example, miRNA-143 is downregulated in 88% of colorectal colon cancers and down-regulation of miRNA-143 causes up-regulation of protein expression of its target oncogene KRAS as well as its target DNA methylating protein DNMT3A.

• #72 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Field defects are important in the progression of colon cancer. The term „field cancerization” was first used in 1953 to describe an area or „field” of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards the development of cancer. Since then, the terms „field cancerization”, „field carcinogenesis”, „field defect”, and „field effect” have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise. […] Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. Epigenetic alterations, distinct from mutations, change the protein expression of genes without changing the DNA sequence. One frequent type of epigenetic alteration in colorectal cancers is changed expression levels of particular microRNAs. microRNAs (miRNAs) are small RNAs that bind the 3 untranslated regions of their target messenger RNAs and cause suppression of protein translation. Down-regulation or up-regulation of microRNAs are epigenetic alterations since their altered regulation of messenger RNAs does not directly involve changing the DNA sequence. microRNAs are important epigenetic factors in colorectal cancer, with 164 microRNAs significantly altered in colorectal cancers. miRNAs have an average of 300 target genes per miRNA. About 60% of human protein-coding genes appear to be under the epigenetic control of miRNAs. As an example, miRNA-143 is downregulated in 88% of colorectal colon cancers and down-regulation of miRNA-143 causes up-regulation of protein expression of its target oncogene KRAS as well as its target DNA methylating protein DNMT3A.

• #73 Colorectal Carcinoma pathogenesis and clinical findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/colorectal-carcinoma-pathogenesis-and-clinical-findings/colorectal-carcinoma/

  Colorectal Carcinoma: Pathogenesis and clinical findings […] Colorectal Carcinoma (Develops over time) […] Tumor Spread Mechanisms: 1. Hematogenous 2. Lymphatic 3. Contiguous 4. Transperitoneal […] Host immune cells release cytokines to combat cancer […] Tumors develop in liver, lungs, brain, peritoneum and lymph nodes.

• #74 Colorectal Carcinoma pathogenesis and clinical findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/colorectal-carcinoma-pathogenesis-and-clinical-findings/colorectal-carcinoma/

  Colorectal Carcinoma: Pathogenesis and clinical findings […] Colorectal Carcinoma (Develops over time) […] Tumor Spread Mechanisms: 1. Hematogenous 2. Lymphatic 3. Contiguous 4. Transperitoneal […] Host immune cells release cytokines to combat cancer […] Tumors develop in liver, lungs, brain, peritoneum and lymph nodes.

• #75

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  The pathway of CpG island methylator phenotype is described by the global hypermethylation of promoter CpG island sites, which also results in the inactivation of tumour suppressor genes. […] However, these pathways do not occur in isolation but overlap to some extent. […] In the conceptualisation of these pathways, although there are still some uncertainties in the molecular mechanisms underlying the development of colorectal tumours from early lesions to advanced ones, most bowel cancers develop slowly from adenomatous polyps or flat adenomas. […] Cancer metastasis is the process whereby primary tumour cells spread from the original tumour site and establish secondary tumour colonies in distant organs. […] The most common site of metastasis from bowel cancer is the liver, and this is often the only site where metastasis is observed.

• #76 Colorectal Cancer – Gastrointestinal Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/gastrointestinal-disorders/tumors-of-the-gastrointestinal-tract/colorectal-cancer

  Colorectal cancer (CRC) most often occurs as transformation within adenomatous polyps. About 80% of cases are sporadic, and 20% have an inheritable component. Many genetic syndromes predispose to CRC: […] Predisposing medical conditions include chronic inflammatory disorders (eg, ulcerative colitis, Crohn colitis); the risk of cancer increases with the duration of these disorders. […] Carcinogens may be ingested in the diet but are more likely produced by bacterial action on dietary substances or biliary or intestinal secretions. The exact mechanism is unknown. […] CRC spreads by direct extension through the bowel wall, hematogenous metastasis, regional lymph node metastasis, and perineural spread.

• #77 Colorectal Carcinoma pathogenesis and clinical findings | Calgary Guide

  https://calgaryguide.ucalgary.ca/colorectal-carcinoma-pathogenesis-and-clinical-findings/colorectal-carcinoma/

  Colorectal Carcinoma: Pathogenesis and clinical findings […] Colorectal Carcinoma (Develops over time) […] Tumor Spread Mechanisms: 1. Hematogenous 2. Lymphatic 3. Contiguous 4. Transperitoneal […] Host immune cells release cytokines to combat cancer […] Tumors develop in liver, lungs, brain, peritoneum and lymph nodes.

• #78

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  Upon encountering the vessels, the tumour cells enter circulatory systems through a process called intravasation. […] When primary tumour cells successfully migrate into the blood stream through intravasation, they become circulating tumour cells (CTCs) and are considered as one of the main biomarkers for metastatic spread. […] The entire cycle of bowel cancer metastasis is graphically presented in Fig. 3. […] The observed changes in the mechanical response of cancer tissues may allow the identification of specific mechanical markers. […] In particular, stiffness could be a new mechanomarker for bowel cancer and potentially for the other bowel pathologies as well. […] In summary, it is clear that, despite improvements in bowel cancer screening, detection, staging and treatment over recent years, there remains much work to do to meet the global aim of dramatically reducing both the mortality and suffering caused by bowel cancer, and the burden of the disease on patients, families, health systems and societies.

• #79 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  Molecular pathways in colorectal carcinogenesis involve several complex genetic and epigenetic modulations that cause normal colonic mucosa to metamorphose into a benign polyp and subsequently into a malignant tumor. […] In 2015, the molecular classification for colorectal cancers was unified into one system with four distinct groups, also called as consensus molecular subtypes. This led to an enhanced understanding of molecular and immune signatures which has implications on predicting the clinical behavior as well as response to different therapeutic agents. […] Pathogenesis of CRC is multi-phasic, starting from the earliest dysplastic lesion called aberrant crypt focus to adenomatous polyp to invasive cancer. On the molecular level, Vogelstein and colleagues proposed that development of carcinogenesis depends on progressive accumulation of changes beneficial to tumor growth over time leading eventually to an invasive malignancy. This is called the adenoma-carcinoma sequence.

• #80 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Approximately 70% of all human genes are expressed in colorectal cancer, with just over 1% having increased expression in colorectal cancer compared to other forms of cancer. Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated. […] Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF- signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer.

• #81

  https://www.alliedacademies.org/articles/pathogenesis-of-colorectal-cancer-17691.html

  Około 70% wszystkich ludzkich genów jest wyrażanych w raku jelita grubego, z nieco ponad 1% mającym zwiększoną ekspresję w raku jelita grubego w porównaniu z innymi typami nowotworów. […] Szczegółowe badania genomowe ujawniły, że raki jelita grubego można klasyfikować na typy nowotworów hiperzmienionych i nie-hyperzmienionych. […] Wspólnym tematem wśród tych genów, w obu typach nowotworów, jest ich związek w szlakach sygnalizacyjnych Wnt i TGF-β, co prowadzi do zwiększonej aktywności MYC, kluczowego uczestnika w raku jelita grubego.

• #82 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Approximately 70% of all human genes are expressed in colorectal cancer, with just over 1% having increased expression in colorectal cancer compared to other forms of cancer. Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated. […] Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF- signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer.

• #83 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Approximately 70% of all human genes are expressed in colorectal cancer, with just over 1% having increased expression in colorectal cancer compared to other forms of cancer. Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated. […] Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in Wnt and TGF- signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer.

• #84

  https://www.alliedacademies.org/articles/pathogenesis-of-colorectal-cancer-17691.html

  Około 70% wszystkich ludzkich genów jest wyrażanych w raku jelita grubego, z nieco ponad 1% mającym zwiększoną ekspresję w raku jelita grubego w porównaniu z innymi typami nowotworów. […] Szczegółowe badania genomowe ujawniły, że raki jelita grubego można klasyfikować na typy nowotworów hiperzmienionych i nie-hyperzmienionych. […] Wspólnym tematem wśród tych genów, w obu typach nowotworów, jest ich związek w szlakach sygnalizacyjnych Wnt i TGF-β, co prowadzi do zwiększonej aktywności MYC, kluczowego uczestnika w raku jelita grubego.

• #85 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  Gain of function mutations in oncogenes leads to constitutive activation and uncontrolled growth leading to cancer. Several oncogenes have been incriminated in colorectal tumorigenesis. […] According to the adenoma-carcinoma sequence model, as mentioned above, CRC origin is initiated by mutations in the Apc gene. […] TP53 is also known as the gatekeeper of the genome and is a pivotal mutation in a multitude of cancers including colon cancer. […] Mutations in the Phosphatase and Tensin homolog (PTEN) gene are linked with CRC in the young (50 years). […] TGF is a signaling molecule that regulates inhibition of cellular proliferation and induction of apoptosis. […] Over the years, there has been convincing evidence that right and left sided malignancies behave as two clinically disparate entities.

• #86 Molecular Pathogenesis and Classification of Colorectal Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469945/

  At a molecular level, right sided colon cancers (RCRC) are more frequently associated with high microsatellite instability, mismatch repair deficiency, CpG island methylation, and BRAF mutations. […] The tumor microenvironment is comprised of cellular components belonging to the epithelium, stroma as well as the adaptive and innate immune system. […] Advances in gene profiling techniques have paved our way to a better discernment of the discrete as well as interlinked pathways in complex molecular pathogenesis of CRC. […] Amongst these, the adenoma-carcinoma model which is initiated by APC mutation and propagated by chromosomal instability causing stepwise accretion of molecular and epigenetic changes accounts for ~80% cases. The remaining 15-20% of CRCs are developed through an alternative pathway, such as defective mismatch repair systems, hypermethylation of CIMP or BRAF activation.

• #87 Pathogenesis of Colorectal Cancer – Pathology Made Simple

  https://ilovepathology.com/pathogenesis-of-colorectal-cancer/

  APC or Beta-Catenin Pathway: This pathway is activated in the classic adenoma-carcinoma sequence, often due to mutations in the APC gene. Microsatellite Instability (MSI) Pathway: MSI occurs when there are defects in DNA mismatch repair genes, resulting in mutations in microsatellite repeat regions. […] Epigenetic modifications, such as DNA methylation, can induce gene silencing, contributing to cancer development. […] Mutations in the APC gene disrupt the destruction complex, causing an accumulation of beta-catenin and continuous cell proliferation. APC mutations are associated with familial adenomatous polyposis (FAP) and sporadic adenomas. […] MSI is characterized by impaired DNA mismatch repair, resulting in an accumulation of mutations in microsatellite repeat regions. This pathway is often associated with serrated lesions and tumors located on the right side of the colon. […] Colorectal cancer is a multifaceted disease influenced by genetic and dietary factors. Understanding its pathogenesis and risk factors is essential for making informed decisions regarding prevention and early detection.

• #88 Oncoscience | Genetic pathways, prevention, and treatment of sporadic colorectal cancer

  https://www.oncoscience.us/article/59/text/

  The development of sporadic colon cancer is thought to be influenced by diet, lifestyle, environmental factors, and acquired somatic mutations. […] It is well established that sporadic CRC is a genetic disease caused by sequential accumulation of mutations in multiple genes. […] Over the past three decades, molecular genetic studies have identified several crucial gene defects that underlie predisposition to sporadic CRC. […] The majority of sporadic CRCs are due to events that result from aberrations in the CIN pathway. […] The CIN pathway is an adenoma-carcinoma sequence model which suggests that a stepwise pattern of mutational activation of oncogenes and inactivation of tumor suppressor genes result in CRC. […] Among the earliest events in sporadic CRC progression pathway is the loss of the APC gene. Genetic disruption of the APC gene or its inactivation by hypermethylation of the APC promoter leads to Wnt/-catenin signaling activation.

• #89 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Colorectal-Cancer-Pathogenesis.aspx

  Colorectal cancer development begins with the formation of a small fixed adenoma. This progresses into a more advanced, larger fixed adenoma. The tumor further develops into a large carcinoma covering a wide circumference of the colon/rectum. More aggressive forms will grow even bigger and begin to block the lumen of the colon/rectum. […] The development of colorectal cancer is mainly due to genomic and epigenomic instability. Understanding more about its development will improve the diagnostics and treatment of colorectal cancer in the future. […] Both genetic and environmental factors are important in the development of colorectal cancer. […] The hereditary forms of colorectal cancer such as Lynch syndrome are caused by a mutation in one of the DNA mismatch repair genes, which include MLH1, MSH2, MSH6, PMS2, and EPCAM. Mutations in these genes inhibit the ability for proper mismatch repair during replication, causing an accumulation of DNA mutations. This can lead to microsatellite instability.

• #90 Pathogenesis of Colorectal Cancer – Pathology Made Simple

  https://ilovepathology.com/pathogenesis-of-colorectal-cancer/

  Understanding the Pathogenesis of Colorectal Cancer […] Colorectal cancer typically affects individuals between the ages of 60 to 70, although there is a growing incidence among those under 40. […] Reduced intake of unabsorbable vegetable fiber leads to decreased stool bulk and alters the composition of intestinal microbiota. This alteration results in increased synthesis of potentially toxic oxidative byproducts from bacterial metabolism. The diminished stool bulk reduces motility, allowing these harmful byproducts to remain in contact with the colonic mucosa for extended periods, increasing the risk of carcinogenesis. […] A diet rich in refined carbohydrates and fat can enhance the hepatic synthesis of cholesterol and bile acids. These bile acids are subsequently converted into carcinogens by intestinal bacteria.

• #91 Pathogenesis of Colorectal Cancer – Pathology Made Simple

  https://ilovepathology.com/pathogenesis-of-colorectal-cancer/

  Understanding the Pathogenesis of Colorectal Cancer […] Colorectal cancer typically affects individuals between the ages of 60 to 70, although there is a growing incidence among those under 40. […] Reduced intake of unabsorbable vegetable fiber leads to decreased stool bulk and alters the composition of intestinal microbiota. This alteration results in increased synthesis of potentially toxic oxidative byproducts from bacterial metabolism. The diminished stool bulk reduces motility, allowing these harmful byproducts to remain in contact with the colonic mucosa for extended periods, increasing the risk of carcinogenesis. […] A diet rich in refined carbohydrates and fat can enhance the hepatic synthesis of cholesterol and bile acids. These bile acids are subsequently converted into carcinogens by intestinal bacteria.

• #92 Colorectal Cancer Pathogenesis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/15017

  The International Agency for Research on Cancer (WHO-IARC) classified the consumption of processed meat as “carcinogenic to humans.” […] Several compounds present in red (haem iron) and/or processed meat (nitrates and nitrites) as well as those formed during cooking will react with colorectal mucosa and promote carcinogenesis. […] The process of meat cooking can incorporate or develop mutagens and carcinogens, which have been shown to enhance carcinogenesis. […] Moreover, N-nitroso compounds (NOC) obtained by the interaction between nitrogen oxides or nitrite with secondary amines and N-alkillamides have CRC carcinogenic properties. […] The correlation between TMAO and cancer is performed via inflammation, OS, DNA damage, and protein folding disruption. […] An elevated body weight associated with a sedentary lifestyle plays an important role in CRC pathogenesis.

• #93 Colorectal Cancer Pathogenesis | Encyclopedia MDPI

  https://encyclopedia.pub/entry/15017

  The International Agency for Research on Cancer (WHO-IARC) classified the consumption of processed meat as “carcinogenic to humans.” […] Several compounds present in red (haem iron) and/or processed meat (nitrates and nitrites) as well as those formed during cooking will react with colorectal mucosa and promote carcinogenesis. […] The process of meat cooking can incorporate or develop mutagens and carcinogens, which have been shown to enhance carcinogenesis. […] Moreover, N-nitroso compounds (NOC) obtained by the interaction between nitrogen oxides or nitrite with secondary amines and N-alkillamides have CRC carcinogenic properties. […] The correlation between TMAO and cancer is performed via inflammation, OS, DNA damage, and protein folding disruption. […] An elevated body weight associated with a sedentary lifestyle plays an important role in CRC pathogenesis.

• #94 Red Meat Genetic Signature for Colorectal Cancer – NCI

  https://www.cancer.gov/news-events/cancer-currents-blog/2021/red-meat-colorectal-cancer-genetic-signature

  Researchers have identified a consistent pattern of DNA damage in the colorectal tumors of people with frequent consumption of red and processed meat. […] New insights may soon be at hand. Kana Wu, M.D., Ph.D., of the Department of Nutrition at the Harvard T.H. Chan School of Public Health, initiated a study to see if frequent consumption of red and processed meat, a known risk factor for colorectal cancer, may leave a specific pattern of DNA damage, known as a mutational signature, in colorectal tumors. […] The discovery of alkylating mutational signature associated with the consumption of red and processed meats further implicates diet in the development of colorectal cancer, said Marios Giannakis, M.D., Ph.D., also of the Dana-Farber Cancer Institute and Harvard Medical School, who co-led the study, published June 17 in Cancer Discovery.

• #95 Red Meat Genetic Signature for Colorectal Cancer – NCI

  https://www.cancer.gov/news-events/cancer-currents-blog/2021/red-meat-colorectal-cancer-genetic-signature

  Understanding how red and processed meat may cause genetic damage that can lead to colorectal cancer may make it possible to prevent colorectal cancer, detect it early, and treat it with targeted therapies, Dr. Giannakis noted. […] Alkylating signatures are a type of mutational signature that arise when genetic material is damaged by chemicals that form lesions in DNA, a process known as alkylation. […] A possible link could be that if you have high red meat consumption, you get this alkylating damage, and this alkylating damage [causes mutations in] the KRAS genes. […] Normal colorectal tissue also contained alkylating signatures, the researchers found. That could suggest that DNA damage begins long before the cancer starts to form, they wrote. […] What it implies is that you’re probably fine until you get that MGMT defect, and once you do, then red meat is really dangerous. […] Dr. Giannakis said more studies need to be done to better characterize these tumors. […] Ultimately, if we can identify what some of these precursors are, there may be ways to mitigate their formation during cooking or processing of meats, Dr. Turesky said.

• #96 Red Meat Genetic Signature for Colorectal Cancer – NCI

  https://www.cancer.gov/news-events/cancer-currents-blog/2021/red-meat-colorectal-cancer-genetic-signature

  Understanding how red and processed meat may cause genetic damage that can lead to colorectal cancer may make it possible to prevent colorectal cancer, detect it early, and treat it with targeted therapies, Dr. Giannakis noted. […] Alkylating signatures are a type of mutational signature that arise when genetic material is damaged by chemicals that form lesions in DNA, a process known as alkylation. […] A possible link could be that if you have high red meat consumption, you get this alkylating damage, and this alkylating damage [causes mutations in] the KRAS genes. […] Normal colorectal tissue also contained alkylating signatures, the researchers found. That could suggest that DNA damage begins long before the cancer starts to form, they wrote. […] What it implies is that you’re probably fine until you get that MGMT defect, and once you do, then red meat is really dangerous. […] Dr. Giannakis said more studies need to be done to better characterize these tumors. […] Ultimately, if we can identify what some of these precursors are, there may be ways to mitigate their formation during cooking or processing of meats, Dr. Turesky said.

• #97 The colon has a safety mechanism that restricts tumour formation | IRB Barcelona

  https://www.irbbarcelona.org/en/news/the-colon-has-a-safety-mechanism-that-restricts-tumour-formation

  When adenomas appear in the colon, the same cells of the tissue produce a molecule that neutralizes its progression. […] Colon cancer development starts with the formation of benign tumours called adenomas. It is estimated that between 30% and 50% of people over 50 will develop one of these tumours. These adenomas or polyps are the pre-cancerous lesions that, once they accumulate further genetic mutations over many years, can progress to colon cancer. […] The scientists have observed that the formation of an adenoma in the colon is accompanied by an increase in the production of a molecule called BMP (bone morphogenetic protein). The study explains that BMP limits the self-renewal capacity of adenoma stem cells, thus impeding the rapid development of the lesion. […] Colon cancer is a disease that develops slowly and this slowness may be caused by this safety mechanism, says Eduard Batlle, head of the Colorectal Cancer Laboratory at IRB Barcelona whose research interests include the study of how colon cancers arise and how they become malignant.

• #98 The colon has a safety mechanism that restricts tumour formation | IRB Barcelona

  https://www.irbbarcelona.org/en/news/the-colon-has-a-safety-mechanism-that-restricts-tumour-formation

  When adenomas appear in the colon, the same cells of the tissue produce a molecule that neutralizes its progression. […] Colon cancer development starts with the formation of benign tumours called adenomas. It is estimated that between 30% and 50% of people over 50 will develop one of these tumours. These adenomas or polyps are the pre-cancerous lesions that, once they accumulate further genetic mutations over many years, can progress to colon cancer. […] The scientists have observed that the formation of an adenoma in the colon is accompanied by an increase in the production of a molecule called BMP (bone morphogenetic protein). The study explains that BMP limits the self-renewal capacity of adenoma stem cells, thus impeding the rapid development of the lesion. […] Colon cancer is a disease that develops slowly and this slowness may be caused by this safety mechanism, says Eduard Batlle, head of the Colorectal Cancer Laboratory at IRB Barcelona whose research interests include the study of how colon cancers arise and how they become malignant.

• #99 The colon has a safety mechanism that restricts tumour formation | IRB Barcelona

  https://www.irbbarcelona.org/en/news/the-colon-has-a-safety-mechanism-that-restricts-tumour-formation

  When adenomas appear in the colon, the same cells of the tissue produce a molecule that neutralizes its progression. […] Colon cancer development starts with the formation of benign tumours called adenomas. It is estimated that between 30% and 50% of people over 50 will develop one of these tumours. These adenomas or polyps are the pre-cancerous lesions that, once they accumulate further genetic mutations over many years, can progress to colon cancer. […] The scientists have observed that the formation of an adenoma in the colon is accompanied by an increase in the production of a molecule called BMP (bone morphogenetic protein). The study explains that BMP limits the self-renewal capacity of adenoma stem cells, thus impeding the rapid development of the lesion. […] Colon cancer is a disease that develops slowly and this slowness may be caused by this safety mechanism, says Eduard Batlle, head of the Colorectal Cancer Laboratory at IRB Barcelona whose research interests include the study of how colon cancers arise and how they become malignant.

• #100 The colon has a safety mechanism that restricts tumor formation

  https://medicalxpress.com/news/2014-06-colon-safety-mechanism-restricts-tumor.html

  Colon cancer development starts with the formation of benign tumours called adenomas. It is estimated that between 30% and 50% of people over 50 will develop one of these tumours. These adenomas or polyps are the pre-cancerous lesions that, once they accumulate further genetic mutations over many years, can progress to colon cancer. […] The scientists have observed that the formation of an adenoma in the colon is accompanied by an increase in the production of a molecule called BMP (bone morphogenetic protein). The study explains that BMP limits the self-renewal capacity of adenoma stem cells, thus impeding the rapid development of the lesion. […] Colon cancer is a disease that develops slowly and this slowness may be caused by this safety mechanism. […] One hypothesis that has arisen from the study is that we are not equally protected and that there are genetic variations in the population that determine that some people have more robust safety mechanisms to respond to polyp formation than others.

• #101 The colon has a safety mechanism that restricts tumour formation | IRB Barcelona

  https://www.irbbarcelona.org/en/news/the-colon-has-a-safety-mechanism-that-restricts-tumour-formation

  We provide a plausible explanation of why certain genomic variations (called snip SNP-) are associated with a greater risk of colon cancer and we believe it is because these variations affect this safety system that protects us from adenomas, explain the scientists. […] A better understanding of the mechanism that accelerates or restricts the development of cancer may allow, for example, the discovery of new biomarkers to better identify the population at greatest risk of colon cancer and even the current degree of risk.

• #102 The colon has a safety mechanism that restricts tumor formation

  https://medicalxpress.com/news/2014-06-colon-safety-mechanism-restricts-tumor.html

  These genomic variations have been revealed by studies in the population and by analysis of the genomes of colon cancer patients that are available in data bases such as that of the 1000 Genomes Project Data. […] We provide a plausible explanation of why certain genomic variations (called snip – SNP-) are associated with a greater risk of colon cancer and we believe it is because these variations affect this safety system that protects us from adenomas. […] A better understanding of the mechanism that accelerates or restricts the development of cancer may allow, for example, the discovery of new biomarkers to better identify the population at greatest risk of colon cancer and even the current degree of risk.

• #103 The colon has a safety mechanism that restricts tumour formation | IRB Barcelona

  https://www.irbbarcelona.org/en/news/the-colon-has-a-safety-mechanism-that-restricts-tumour-formation

  We provide a plausible explanation of why certain genomic variations (called snip SNP-) are associated with a greater risk of colon cancer and we believe it is because these variations affect this safety system that protects us from adenomas, explain the scientists. […] A better understanding of the mechanism that accelerates or restricts the development of cancer may allow, for example, the discovery of new biomarkers to better identify the population at greatest risk of colon cancer and even the current degree of risk.

• #104 The colon has a safety mechanism that restricts tumor formation

  https://medicalxpress.com/news/2014-06-colon-safety-mechanism-restricts-tumor.html

  These genomic variations have been revealed by studies in the population and by analysis of the genomes of colon cancer patients that are available in data bases such as that of the 1000 Genomes Project Data. […] We provide a plausible explanation of why certain genomic variations (called snip – SNP-) are associated with a greater risk of colon cancer and we believe it is because these variations affect this safety system that protects us from adenomas. […] A better understanding of the mechanism that accelerates or restricts the development of cancer may allow, for example, the discovery of new biomarkers to better identify the population at greatest risk of colon cancer and even the current degree of risk.

• #105

  https://link.springer.com/article/10.1007/s10439-023-03155-8

  It is therefore imperative when engineering robotic devices for diagnosis to understand the mechanisms involved in the spread of cancer cells from the primary tumour site to distant organs and the potential difficulties encountered. […] The processes in which new blood and lymphatic vessels form is called angiogenesis and lymphangiogenesis, respectively. […] Once a primary bowel tumour reaches a volume of approximately 2 mm3, it relies on the formation of new vascular networks to provide a suitable supply of nutrients and oxygen and facilitate the removal of waste. […] To gain access to the blood stream, cancer cells must first detach from the tumour and invade through the extracellular matrix or infiltrate local tissue. […] Epithelial mesenchymal transition is the process in which tumour associated epithelial cells change phenotype and transform to acquire more invasive and metastatic mesenchymal cell properties.

• #106 Colorectal Cancer – From Pathogenesis to Treatment | IntechOpen

  https://www.intechopen.com/books/5122

  Colorectal cancer (CRC) is a major health problem because it represents around 10% of all cancers and achieves a worldwide estimate of 1.4 million newly diagnosed cases annually, resulting in approximately 700,000 deaths. […] A better understanding of the biology of the tumor, along with high efficiency of diagnostic and therapeutic methods, as well as the spread of screening programs, will improve the survival of the CRC patients in the near future. […] Molecular Mechanisms Involved in the Acquisition of Resistance to Treatment of Colon Cancer Cells. […] Circadian Regulation of Colon Cancer Stem Cells: Implications for Therapy. […] Modulation of Apoptosis in Colon Cancer Cells by Bioactive Compounds. […] BRAF Mutation in Colorectal Cancer. […] Current Immunotherapeutic Treatments in Colon Cancer. […] Anti-Epidermal Growth Factor Receptor (EGFR) Treatment in Patients with Metastatic Colorectal Cancer. […] Adjuvant Treatment in Colon Cancer. […] Immunotherapy in Colorectal Cancer.

• #107 Analyzing and validating the prognostic value and mechanism of colon cancer immune microenvironment | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02491-w

  Colon cancer is a disease with high malignancy and incidence in the world. Tumor immune microenvironment (TIM) and tumor mutational burden (TMB) have been proved to play crucial roles in predicting clinical outcomes and therapeutic efficacy, but the correlation between them and the underlying mechanism were not completely understood in colon cancer. […] The colon cancer patients were clustered into low immunity, median immunity and high immunity groups. The median immunity group had a favorable survival probability compared with that of the low and high immunity groups. […] We performed a comprehensive evaluation of the immune microenvironment landscape of colon cancer and demonstrated the positive correlation between immunity and TMB. […] The essence of tumor immunotherapy is to arouse and strengthen the immune system to kill tumor cells in various ways. Tumor mutational burden (TMB) was defined as the total amount of coding errors of somatic genes, base substitutions, insertions or deletions detected across per million bases.

• #108 Colorectal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Colorectal_cancer

  Epigenetic reductions of DNA repair enzyme expression may likely lead to the genomic and epigenomic instability characteristic of cancer. As summarized in the articles Carcinogenesis and Neoplasm, for sporadic cancers in general, a deficiency in DNA repair is occasionally due to a mutation in a DNA repair gene, but is much more frequently due to epigenetic alterations that reduce or silence expression of DNA repair genes. […] Epigenetic alterations involved in the development of colorectal cancer may affect a person’s response to chemotherapy.

• #109

  https://grantome.com/grant/NIH/R01-CA155019-01A1

  This proposed project will provide the molecular basis for developing miR-140-based therapeutic strategies to overcome chemoresistance in colon cancer stem cells and to improve patient survival. […] This project will help to develop a new paradigm in our current understanding of the tumor biology as it relates to miR-140 function. […] This, in turn, may lead to the development of novel targeted therapies to colon cancer stem cells and enhance our understanding of chemoresistance in cancer, which fits the scope of the National Cancer Institute’s mission to eliminate cancer.

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