Materiały źródłowe

• #1 Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances

  https://www.mdpi.com/2072-6694/14/3/621

  Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis, without major therapeutic improvement for years and increasing incidence. […] The cell of origin of HCC remains elusive, probably due to the heterogeneity of liver cancer within the same tumor and between different tumors. […] About 70–80% of HCC develop in a context of cirrhosis that involves a complex multistep process. […] HCC arises from the accumulation of somatic mutations and epigenomic alterations. […] The WNT-β-catenin pathway is frequently activated in HCC due to mutations in AXIN1 and CTNNB1. […] The interaction of the microenvironment with the tumor plays a relevant role in HCC pathogenesis. […] Tumor microenvironment plays a critical role in HCC progression.

• #2 Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

  https://www.mdpi.com/2227-9059/10/12/3202

  Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. […] In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC.

• #3 Pathogenesis to management of hepatocellular carcinoma

  https://medicalxpress.com/news/2023-01-pathogenesis-hepatocellular-carcinoma.html

  A new review was published in Genes & Cancer on December 13, 2022, entitled, „Pathogenesis to management of hepatocellular carcinoma.” In this review, researchers from multiple universities and medical centers across the U.S. discussed hepatocellular carcinoma (HCC)—the most common primary liver cancer, whose incidence continues to rise in many parts of the world due to a concomitant rise in many associated risk factors, such as alcohol use and obesity. […] Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of cancer death. Although early-stage HCC can be potentially curable through liver resection, liver-directed therapies, or transplantation, patients usually present with intermediate to advanced disease, which continues to be associated with a poor prognosis. This is because HCC is a cancer with significant complexities, including substantial clinical, histopathologic, and genomic heterogeneity. However, the scientific community has made a major effort to better characterize HCC in those aspects via utilizing tissue sampling and histological classification, whole genome sequencing, and developing viable animal models.

• #4 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process involving the progressive accumulation of molecular alterations pinpointing different molecular and cellular events. […] There is emerging evidence supporting the importance of cancer metabolism and tumor microenvironment in providing a favorable and supportive niche to expedite HCC development. […] Moreover, recent studies have identified distinct surface markers of cancer stem cell (CSC) in HCC, and they also put forward the profound involvement of altered signaling pathways and epigenetic modifications in CSCs, in addition to the concomitant drug resistance and metastasis. […] Taken together, multiple key genetic and non-genetic factors, as well as liver CSCs, result in the development and progression of HCC.

• #5 Pathogenesis to management of hepatocellular carcinoma

  https://medicalxpress.com/news/2023-01-pathogenesis-hepatocellular-carcinoma.html

  A new review was published in Genes & Cancer on December 13, 2022, entitled, „Pathogenesis to management of hepatocellular carcinoma.” In this review, researchers from multiple universities and medical centers across the U.S. discussed hepatocellular carcinoma (HCC)—the most common primary liver cancer, whose incidence continues to rise in many parts of the world due to a concomitant rise in many associated risk factors, such as alcohol use and obesity. […] Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of cancer death. Although early-stage HCC can be potentially curable through liver resection, liver-directed therapies, or transplantation, patients usually present with intermediate to advanced disease, which continues to be associated with a poor prognosis. This is because HCC is a cancer with significant complexities, including substantial clinical, histopathologic, and genomic heterogeneity. However, the scientific community has made a major effort to better characterize HCC in those aspects via utilizing tissue sampling and histological classification, whole genome sequencing, and developing viable animal models.

• #6 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  Among the identified etiological risk factors for HCC, which include chronic viral infections (HBV and hepatitis C virus), chronic alcohol consumption, and non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, chronic HBV infection accounts for around 50% of the cases. […] The resultant enhanced survival, proliferation and reduction in apoptosis may lead to an imbalance of the overall oncogenic and tumor suppressive signals, thus supporting HCC development. […] Epigenetic alterations are reversible modifications at the genome level without involving changes of the DNA sequence. […] The valuable information generated by various genomic, transcriptomic and epigenetic alterations provide us with a comprehensive assessment about how these changes may affect key signaling pathways supporting the development of HCC.

• #7 Hepatocellular carcinoma pathogenesis: from genes to environment | Nature Reviews Cancer

  https://www.nature.com/articles/nrc1934

  Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and affects many of the world’s populations. […] Various aetiologies have been linked to HCC development, the most prominent of which include chronic hepatitis B (HBV) and C (HCV) viral infection, chronic alcohol consumption and aflatoxin-B1-contaminated food. Virtually all cirrhosis-inducing conditions can cause HCC, pointing to important interactions with the host microenvironment. […] HBV-induced hepatocarcinogenesis can involve an array of processes, including host-viral interactions, sustained cycles of necrosis-inflammation-regeneration, viral-endoplasmic-reticulum interactions (induction of oxidative stress), viral integration into the host genome (and associated host DNA deletions) and the targeted activation of oncogenic pathways by various viral proteins.

• #8 Introductory Chapter: Etiology and Pathogenesis of Hepatocellular Carcinoma | IntechOpen

  https://www.intechopen.com/chapters/61816

  Hepatocellular carcinoma (HCC) is the most frequent malignant tumor of the liver with hundreds of thousands of new cases diagnosed each year. […] HCC has several well-known risk factors, which have been proven to strongly associate with the development of HCC. The most common etiological risk factors are hepatotropic viruses: hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) and a suggestive evidence is revealed by similar distribution of HCC in areas where these viruses also encounter increasing incidence and it is considered that up to 90% of the diagnosed HCCs develop in context of hidden cirrhosis. […] Cirrhosis is the main underlying cause for most HCC cases, with HBV, and HCV infection often involved in the development of cirrhosis. Approximately 70-90% of liver cancers occur on cirrhosis, and in Western countries, the HCC ratio on cirrhosis exceeds 90%.

• #9 Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

  https://www.mdpi.com/2227-9059/10/12/3202

  The prognosis of patients with HCC depends highly on performance status and liver function. Therefore, HCC in liver cirrhosis is classified by the updated Barcelona-Clinic-Liver cancer (BCLC) Classification system. […] The treatment concept is curative in the very early stage (BCLC stage 0) and early stage (BCLC stage A). […] In this regard, it is evident to identify clinical and molecular subtypes for a better tailored and individualized medicine in systemic therapy of HCC. Due to the global disease burden, it is of utmost importance to better understand HCC pathogenesis to develop new treatments and approaches with promising therapeutic targets. […] The common feature of all these factors is induction of liver cirrhosis as a possible complication. […] Chronic hepatitis B or C virus infections, hereditary diseases, e.g., hemochromatosis, α1-antitrypsin deficiency as well as tyrosinemia or glycogen storage disease type 1a play a role in HCC pathogenesis.

• #10 Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances

  https://www.mdpi.com/2072-6694/14/3/621

  Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis, without major therapeutic improvement for years and increasing incidence. […] The cell of origin of HCC remains elusive, probably due to the heterogeneity of liver cancer within the same tumor and between different tumors. […] About 70–80% of HCC develop in a context of cirrhosis that involves a complex multistep process. […] HCC arises from the accumulation of somatic mutations and epigenomic alterations. […] The WNT-β-catenin pathway is frequently activated in HCC due to mutations in AXIN1 and CTNNB1. […] The interaction of the microenvironment with the tumor plays a relevant role in HCC pathogenesis. […] Tumor microenvironment plays a critical role in HCC progression.

• #11 Introductory Chapter: Etiology and Pathogenesis of Hepatocellular Carcinoma | IntechOpen

  https://www.intechopen.com/chapters/61816

  Hepatocellular carcinoma (HCC) is the most frequent malignant tumor of the liver with hundreds of thousands of new cases diagnosed each year. […] HCC has several well-known risk factors, which have been proven to strongly associate with the development of HCC. The most common etiological risk factors are hepatotropic viruses: hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) and a suggestive evidence is revealed by similar distribution of HCC in areas where these viruses also encounter increasing incidence and it is considered that up to 90% of the diagnosed HCCs develop in context of hidden cirrhosis. […] Cirrhosis is the main underlying cause for most HCC cases, with HBV, and HCV infection often involved in the development of cirrhosis. Approximately 70-90% of liver cancers occur on cirrhosis, and in Western countries, the HCC ratio on cirrhosis exceeds 90%.

• #12 Introductory Chapter: Etiology and Pathogenesis of Hepatocellular Carcinoma | IntechOpen

  https://www.intechopen.com/chapters/61816

  The progression from cirrhosis to HCC is a complex process. Cirrhosis is the outcome of any chronic hepatic illness and it is outlined by debilitation of regenerative capacity of the liver through declining proliferation of the hepatocytes. […] Telomerase dysfunctions determine chromosomal instability and reduced regenerative liver capacity with decreased hepatocyte regeneration. […] Several mouse models studies have suggested that telomerase dysfunctions have been associated with early-stage liver cancers but not with high-grade HCCs, which tends to indicate that telomere dysfunction cannot determine alone the development and progression of HCC in cirrhotic livers. […] Activation of stellate cells in liver cirrhosis can increase products of oxidative stress, several growth factors as well as cytokines with further roles in reducing hepatocyte regeneration, and development of HCC.

• #13 The Progression of Liver Disease to Liver Cancer – American Liver Foundation

  https://liverfoundation.org/resource-center/videos/the-progression-of-liver-disease-to-liver-cancer/

  Liver cancers are 4th most common cause of cancer-related deaths worldwide and it is the 2nd most lethal cancer. […] In fact, the death rate in the US has increased by more than 40% within the last two decades. […] There are many factors that can contribute, including genetic predisposition, family history, environmental exposure, and age and many others, but the underlying theme is that an HCC typically arises from an already damaged liver. […] The pathogenesis of a liver disease becoming an HCC is a complex multi-step process. […] When a liver gets damaged, the liver tries to regenerate and replace the damaged cells. This repair process involves production of collagen which are fibers that stiffen the cells. Chronic liver disease leads to persistent activation of this repair process. It will make the liver more and more stiffer, and all the collagen will replace the healthy cells. This is what we typically call a scarring of the liver, or fibrosis.

• #14 The Progression of Liver Disease to Liver Cancer – American Liver Foundation

  https://liverfoundation.org/resource-center/videos/the-progression-of-liver-disease-to-liver-cancer/

  If left untreated, this scarring will continue to a severely scarred state of the liver, and we call that a cirrhosis. […] Cirrhotic livers are more prone to accumulate DNA mutations. These mutations interfere with the normal cell cycle (such as the growth and division of cells) and the cells instead of regenerating properly, will accumulate together to form nodules. These are called dysplastic nodules and they are pre-cancerous. […] Additional damage and prolonged inflammation will provide these abnormal cells with proliferative, invasive, and survival advantages. including evading the body’s immune system, having an exclusive vascular supply to grow unchecked, and essentially becoming immortal cancer cells. Progressively, the dysplastic nodules transform into ultimately a hepatocellular carcinoma.

• #15 The Progression of Liver Disease to Liver Cancer – American Liver Foundation

  https://liverfoundation.org/resource-center/videos/the-progression-of-liver-disease-to-liver-cancer/

  If left untreated, this scarring will continue to a severely scarred state of the liver, and we call that a cirrhosis. […] Cirrhotic livers are more prone to accumulate DNA mutations. These mutations interfere with the normal cell cycle (such as the growth and division of cells) and the cells instead of regenerating properly, will accumulate together to form nodules. These are called dysplastic nodules and they are pre-cancerous. […] Additional damage and prolonged inflammation will provide these abnormal cells with proliferative, invasive, and survival advantages. including evading the body’s immune system, having an exclusive vascular supply to grow unchecked, and essentially becoming immortal cancer cells. Progressively, the dysplastic nodules transform into ultimately a hepatocellular carcinoma.

• #16 Hepatocellular carcinoma pathogenesis: from genes to environment | Nature Reviews Cancer

  https://www.nature.com/articles/nrc1934

  Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and affects many of the world’s populations. […] Various aetiologies have been linked to HCC development, the most prominent of which include chronic hepatitis B (HBV) and C (HCV) viral infection, chronic alcohol consumption and aflatoxin-B1-contaminated food. Virtually all cirrhosis-inducing conditions can cause HCC, pointing to important interactions with the host microenvironment. […] HBV-induced hepatocarcinogenesis can involve an array of processes, including host-viral interactions, sustained cycles of necrosis-inflammation-regeneration, viral-endoplasmic-reticulum interactions (induction of oxidative stress), viral integration into the host genome (and associated host DNA deletions) and the targeted activation of oncogenic pathways by various viral proteins.

• #17 Molecular mechanism of hepatocellular carcinoma

  https://www.oaepublish.com/articles/2394-5079.2018.23

  Hepatocellular carcinoma (HCC) is characterized by a highly heterogenetic pathogenesis with an aggressive clinical course leading to poor survival. […] It is generally accepted that hepatocarcinogenesis is very complex and occurs through a multistep biological process during malignant transformation of normal hepatocytes in which various factors, including genetic and epigenetic alterations, are involved. […] Chronic HBV infection enables viral DNA to integrate into the host genome, leading to an oncogenic transformation. […] These findings suggest a significant association between HBV integration and hepatocarcinogenesis. […] Accumulating evidence has shown that HBx plays important roles in hepatocarcinogenesis. […] Several mechanisms by which HBx may function at the molecular and cellular levels are as follows: (1) transactivation of promoters of cAMP response element binding protein (CREB) response element (CRE)-containing genes, including the oncogene Yes-associated protein (YAP); (2) alteration of the DNA specificity of CREB and activating transcription factor 2 (ATF-2), resulting in binding and activation of the HBV enhancer; (3) modulation of the DNA binding specificity of the p53 tumor suppressor, resulting in altered expression of its target genes; and (4) regulation of cellular signaling pathways, such as activation of the Ras-Raf-MAPK pathway, Src-dependent pathway, PI3K-Akt pathway, inflammation-associated NF-kB/STAT-3 pathways, and wnt/-catenin pathway.

• #18 Molecular mechanism of hepatocellular carcinoma

  https://www.oaepublish.com/articles/2394-5079.2018.23

  HCV is a major risk factor of HCC, and that chronic HCV infection induces liver fibrosis and cirrhosis, ultimately resulting in HCC. […] Several studies have provided evidence for a direct role of HCV in the pathogenesis of HCC. […] Chronic HCV infection induces oncogenic transformation in several ways: vigorous and continuous inflammation via NF-kB; oxidative stress, inducing DNA mutagenesis; alteration of tumor suppressor genes; direct alteration of the wnt/-catenin pathway by NS5A; and blocking of TGF- signaling through an interaction between TGF- receptor I (TR-I) and NS5A. […] Alcohol consumption, particularly over-consumption, is a serious global health problem. […] In general, heavy alcohol consumption leads to fatty liver, alcoholic steatohepatitis (ASH), cirrhosis, and eventually, HCC.

• #19 Hepatocellular carcinoma pathogenesis: from genes to environment | Nature Reviews Cancer

  https://www.nature.com/articles/nrc1934

  HCV-induced hepatocarcinogenesis also provokes similar biological processes, but is associated with a propensity of HCV to evade the host’s immune responses and to promote cirrhosis. […] Alcohol-induced hepatocarcinogenesis is associated with the induction of inflammation and, consequently, cycles of hepatocyte necrosis and regeneration, oxidative stress and cirrhosis. Aflatoxin-B1-induced hepatocarcinogenesis is mostly associated with carcinogenic mutations. […] Various genetic events have been associated with the development of HCC, such as the inactivation of the tumour suppressor p53, mutations in -catenin, overexpression of various ErbB receptor family members and overexpression of the Met receptor. In addition, various cancer-relevant genes seem to be targeted on the epigenetic level (methylation) in human HCC.

• #20 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  Molecular alterations at both genetic and epigenetic levels have been shown to drive hepatocarcinogenesis. […] Genome instability is a key driver in human cancers including HCC, and this may result in CNAs with gain or loss in chromosomes of different extents or somatic mutations in the genomes. […] Recently, active NGS-based genome-wide mutational screenings in HCC samples with different etiological backgrounds have been carried out worldwide. […] CTNNB1 and TP53 are the most commonly mutated genes in HCC. […] Recently, Schulze et al. took an integrative approach to assess the somatic mutations and focal CNAs in human HCCs to look for gene targets which are frequently and significantly altered through different mechanisms. […] A part from the aforementioned putative HCC drivers affecting a wide spectrum of cellular processes, emerging evidence has indicated frequent and recurrent somatic mutations in the promoter area of the TERT (telomerase reverse transcriptase) in various types of cancer.

• #21 Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances

  https://www.mdpi.com/2072-6694/14/3/621

  Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis, without major therapeutic improvement for years and increasing incidence. […] The cell of origin of HCC remains elusive, probably due to the heterogeneity of liver cancer within the same tumor and between different tumors. […] About 70–80% of HCC develop in a context of cirrhosis that involves a complex multistep process. […] HCC arises from the accumulation of somatic mutations and epigenomic alterations. […] The WNT-β-catenin pathway is frequently activated in HCC due to mutations in AXIN1 and CTNNB1. […] The interaction of the microenvironment with the tumor plays a relevant role in HCC pathogenesis. […] Tumor microenvironment plays a critical role in HCC progression.

• #22 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  Molecular alterations at both genetic and epigenetic levels have been shown to drive hepatocarcinogenesis. […] Genome instability is a key driver in human cancers including HCC, and this may result in CNAs with gain or loss in chromosomes of different extents or somatic mutations in the genomes. […] Recently, active NGS-based genome-wide mutational screenings in HCC samples with different etiological backgrounds have been carried out worldwide. […] CTNNB1 and TP53 are the most commonly mutated genes in HCC. […] Recently, Schulze et al. took an integrative approach to assess the somatic mutations and focal CNAs in human HCCs to look for gene targets which are frequently and significantly altered through different mechanisms. […] A part from the aforementioned putative HCC drivers affecting a wide spectrum of cellular processes, emerging evidence has indicated frequent and recurrent somatic mutations in the promoter area of the TERT (telomerase reverse transcriptase) in various types of cancer.

• #23 Hepatocellular Carcinoma (HCC): Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/197319-overview

  Some of the factors associated with the development of HCC in HBV-infected individuals are as follows: Elevated serum HBV DNA viral load; HBV genotype Risk of HCC appears to be higher with HBV genotypes C and F; HBV mutations Such as in preS, basic core promoter (BCP), or HBx regions; Host factors Such as polymorphisms in KIF1B, HLA-DQ, STAT4, and GRIK1; HBV integration into growth-control genes (eg, TERT), pro-oncogenic genes, or tumor suppressor genes and the oncogenic activity of truncated HBx. […] Genomic sequencing studies for HCC have been performed, and potential driver genes in HCC have been catalogued. Frequently mutated genes identified in large-scale studies, and their functions, include the following: TERT – Maintaining telomere length; TP53 – Tumor suppressor; CTNNB1 – Transcriptional regulator; ARID1A, ARID2 – Chromatin remodeling.

• #24 Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

  https://www.mdpi.com/2227-9059/10/12/3202

  In addition, lifestyle components, such as excessive alcohol consumption or nicotine abuse, favor the development of this neoplasia. […] The Wnt/β-catenin pathway is one of the best-studied signaling cascades. […] WNT/β-catenin signaling is severely disrupted in most HCC cases. Somatic mutations account for about 40 to 60% of a disordered Wnt/β-catenin signaling. […] The most prevalent mutations are in CTNNB1, which destabilizes and translocates β-catenin into the nucleus. […] In summary, CNNTB1, AXIN1/2, and APC mutations result in persistent aberrant activation of the Wnt/β-catenin pathway. […] The JAK/STAT signaling pathway has a pivotal role in various cellular functions and can be activated by different cytokines and growth factors, such as interleukins, interferons, and EGFs.

• #25 Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

  https://www.mdpi.com/2227-9059/10/12/3202

  In addition, lifestyle components, such as excessive alcohol consumption or nicotine abuse, favor the development of this neoplasia. […] The Wnt/β-catenin pathway is one of the best-studied signaling cascades. […] WNT/β-catenin signaling is severely disrupted in most HCC cases. Somatic mutations account for about 40 to 60% of a disordered Wnt/β-catenin signaling. […] The most prevalent mutations are in CTNNB1, which destabilizes and translocates β-catenin into the nucleus. […] In summary, CNNTB1, AXIN1/2, and APC mutations result in persistent aberrant activation of the Wnt/β-catenin pathway. […] The JAK/STAT signaling pathway has a pivotal role in various cellular functions and can be activated by different cytokines and growth factors, such as interleukins, interferons, and EGFs.

• #26 Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

  https://www.mdpi.com/2227-9059/10/12/3202

  In HCC, the JAK/STAT signaling pathway is constitutively activated. […] The transforming growth factor-β (TGF-β) signaling pathway regulates various physiological aspects in embryogenesis and adult tissue homeostasis. […] TGF-β has a dual role of suppressing early stages of tumorigenesis but contributing to the migration and metastasis of HCC.

• #27 Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

  https://www.mdpi.com/2227-9059/10/12/3202

  In HCC, the JAK/STAT signaling pathway is constitutively activated. […] The transforming growth factor-β (TGF-β) signaling pathway regulates various physiological aspects in embryogenesis and adult tissue homeostasis. […] TGF-β has a dual role of suppressing early stages of tumorigenesis but contributing to the migration and metastasis of HCC.

• #28

  https://link.springer.com/article/10.1186/s43556-024-00184-0

  From an overarching perspective, the tumor microenvironment (TME) of HCC comprising cancer cells, immune cells, cytokines, and the extracellular matrix is crucial in facilitating signaling pathways that promote tumors and aid in developing resistance to treatment. […] Therefore, investigating the molecular basis of the pathogenesis of liver cancer, especially HCC, and identifying potential therapeutic targets is crucial for developing interventions or effective treatment strategies, enhancing the prognosis of patients. […] Given the complexity of HCC pathogenesis, targeted therapy remains immature and the application is highly limited despite numerous studies underway. […] This review aims to collate information on pro-tumor pathways of liver cancer and the progression of pathway-specific inhibitors, thereby offering insights for the future development of targeted therapies. […] Overall, this review highlights potential avenues for future advancements in the targeted therapy of liver cancer.

• #29 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  With efforts from studies pinpointing the multiple aspects of HCC pathogenesis, knowledge has been accumulating on the stochastic molecular alterations targeting different cancer hallmark events. […] More importantly, the cancer stem cell (CSC) theory which has emerged in recent decades, together with the traditional clonal evolution model, helps to explain the underlying molecular mechanisms of HCC to a better extent, particularly in the context of tumor relapse, chemoresistance and metastasis. […] The intimate relationship between tumor microenvironment and cancer metabolism has been explored in a number of studies and new data are rapidly emerging. […] In HCC, hypoxia-inducible factor (HIF)-1-induced glycolysis is associated with biological aggressiveness. […] As a consequence, CSCs are believed to play a crucial role in tumor initiation and tumor relapse clinically.

• #30 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  With efforts from studies pinpointing the multiple aspects of HCC pathogenesis, knowledge has been accumulating on the stochastic molecular alterations targeting different cancer hallmark events. […] More importantly, the cancer stem cell (CSC) theory which has emerged in recent decades, together with the traditional clonal evolution model, helps to explain the underlying molecular mechanisms of HCC to a better extent, particularly in the context of tumor relapse, chemoresistance and metastasis. […] The intimate relationship between tumor microenvironment and cancer metabolism has been explored in a number of studies and new data are rapidly emerging. […] In HCC, hypoxia-inducible factor (HIF)-1-induced glycolysis is associated with biological aggressiveness. […] As a consequence, CSCs are believed to play a crucial role in tumor initiation and tumor relapse clinically.

• #31 Proteomics Studies Reveal Mechanisms of Liver Cancer Development – Creative Proteomics

  https://www.creative-proteomics.com/tumomics/proteomics-studies-reveal-mechanisms-of-liver-cancer-development.htm

  More importantly, the clinical prognosis of the three subtypes is significantly different, and its prognostic value does not depend on the commonly used TNM staging in the clinic, which is expected to provide guidance for personalized accurate treatment of liver cancer and clinical prognosis judgment. […] Finally, the study systematically revealed the important role of metabolic abnormalities in the development of liver cancer. The authors found that 80.3% of liver-specific proteins are down-regulated in tumors and are mainly involved in liver-specific metabolic pathways such as gluconeogenesis, detoxification and urea-ammonia metabolism, while key enzymes for cholesterol metabolism and glutamine metabolism-related proteins Expression is upregulated in tumors. […] The study also systematically explained the changing trends of various cellular metabolism and signaling pathways in liver cancer from the multi-omics level.

• #32 Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

  https://www.bmbreports.org/journal/view.html?doi=10.5483/BMBRep.2023-0010

  Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. […] Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. […] Inflammation not only evokes necrosis and genetic alterations in hepatocytes but also leads to fibrosis and cirrhosis, which trigger alterations of the microenvironment and may further contribute to the development of hepatocellular carcinoma (HCC). […] The interactions between the tumor and the tumor microenvironment (TME) play a critical role in cell differentiation, tumorigenesis, metastasis, and the efficacy of drug therapies. […] Liver fibrosis results from inflammation that causes epithelial-to-mesenchymal transition (EMT), endothelial-to-mesenchymal transition (EndMT), and polarization of macrophages.

• #33 Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models

  https://www.bmbreports.org/journal/view.html?doi=10.5483/BMBRep.2023-0010

  The activation of HSCs is the key process in hepatic fibrosis, leading to cirrhosis and HCC. […] Increased expression of -smooth muscle actin (-SMA), which is characteristic of HSC activation in tumors, correlates with a worse prognosis for patients with HCC. […] Yet another key factor in promoting fibrosis is transforming growth factor beta (TGF-), a cytokine that increases HSC activation. […] The phenotypic change of an endothelial cells to a mesenchymal cell, which is called the EndMT, is important in tumor formation, metastasis, and fibrosis. […] Tumor-associated macrophages (TAMs), a well-characterized component of the TME, are important for malignant growth because they secrete several cytokines and regulate the immune response to HCC cells. […] The development of chronic inflammation because of the high level of infiltration of macrophages destroys the internal environment of the liver, furthers cirrhosis and fibrosis, and contributes to HCC development and progression.

• #34 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  With efforts from studies pinpointing the multiple aspects of HCC pathogenesis, knowledge has been accumulating on the stochastic molecular alterations targeting different cancer hallmark events. […] More importantly, the cancer stem cell (CSC) theory which has emerged in recent decades, together with the traditional clonal evolution model, helps to explain the underlying molecular mechanisms of HCC to a better extent, particularly in the context of tumor relapse, chemoresistance and metastasis. […] The intimate relationship between tumor microenvironment and cancer metabolism has been explored in a number of studies and new data are rapidly emerging. […] In HCC, hypoxia-inducible factor (HIF)-1-induced glycolysis is associated with biological aggressiveness. […] As a consequence, CSCs are believed to play a crucial role in tumor initiation and tumor relapse clinically.

• #35 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  In HCC, a recent comprehensive study provided insight on the origin of liver CSCs. […] Over the past decade, a number of liver CSC surface markers have been identified, as evidenced by the functional CSC properties. […] Dysregulation of these two pathways has also been found to be associated with the maintenance of liver CSCs. […] The linkage between NF-B and liver CSCs appears to be a promising area of study. […] Despite the emergence of various therapeutic modalities including chemotherapy, targeted therapy and radiotherapy in recent years, the efficacy in eradicating HCC is still unsatisfactory partially attributed to resistance to treatment conferred by liver CSCs. […] Identification of key molecular events and crucial signaling pathways provides insight to devise targeted therapies to treat this cancer.

• #36 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  In HCC, a recent comprehensive study provided insight on the origin of liver CSCs. […] Over the past decade, a number of liver CSC surface markers have been identified, as evidenced by the functional CSC properties. […] Dysregulation of these two pathways has also been found to be associated with the maintenance of liver CSCs. […] The linkage between NF-B and liver CSCs appears to be a promising area of study. […] Despite the emergence of various therapeutic modalities including chemotherapy, targeted therapy and radiotherapy in recent years, the efficacy in eradicating HCC is still unsatisfactory partially attributed to resistance to treatment conferred by liver CSCs. […] Identification of key molecular events and crucial signaling pathways provides insight to devise targeted therapies to treat this cancer.

• #37 Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10135776/

  The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways that are critical for cell survival or death. The balance between apoptosis and autophagy regulates liver cell turnover and maintains intracellular homeostasis. However, the balance is often dysregulated in many cancers, including HCC. Autophagy and apoptosis pathways may be either independent or parallel or one may influence the other. Autophagy may either inhibit or promote apoptosis, thus regulating the fate of the liver cancer cells. […] The development of HCC is associated with some form of cellular death, which may be either programmed (PCD) (such as apoptosis, necroptosis and autophagy-dependent cell death) or non-programmable (such as pyroptosis and necrosis). Apoptosis is probably the commonest cause of PCD.

• #38 Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10135776/

  The abnormal activation of the oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling is associated with HCC. […] The deregulation of Wnt/-catenin signaling is critical in human HCC. […] The role of autophagy and apoptosis in the initiation, progress and metastatic potential is reviewed and the experimental evidence indicating an interplay between the two is extensively analyzed. […] Autophagy is implicated in the initiation and progression of HCC in many ways. It is closely associated with inflammation, which is a critical factor in HCC development. […] The activation of the Wnt/-catenin pathway favors the development of HCC, as previously mentioned. […] The activation of autophagy may lead to the induction of apoptosis and the inhibition of the growth of hepatoma cells. […] The interplay between autophagy and apoptosis may be implicated in the pathogenesis of NASH and ALD. […] The role of ferroptosis in HCC initiation and progression has been extensively reviewed.

• #39 Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10135776/

  The abnormal activation of the oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling is associated with HCC. […] The deregulation of Wnt/-catenin signaling is critical in human HCC. […] The role of autophagy and apoptosis in the initiation, progress and metastatic potential is reviewed and the experimental evidence indicating an interplay between the two is extensively analyzed. […] Autophagy is implicated in the initiation and progression of HCC in many ways. It is closely associated with inflammation, which is a critical factor in HCC development. […] The activation of the Wnt/-catenin pathway favors the development of HCC, as previously mentioned. […] The activation of autophagy may lead to the induction of apoptosis and the inhibition of the growth of hepatoma cells. […] The interplay between autophagy and apoptosis may be implicated in the pathogenesis of NASH and ALD. […] The role of ferroptosis in HCC initiation and progression has been extensively reviewed.

• #40 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  Among the identified etiological risk factors for HCC, which include chronic viral infections (HBV and hepatitis C virus), chronic alcohol consumption, and non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, chronic HBV infection accounts for around 50% of the cases. […] The resultant enhanced survival, proliferation and reduction in apoptosis may lead to an imbalance of the overall oncogenic and tumor suppressive signals, thus supporting HCC development. […] Epigenetic alterations are reversible modifications at the genome level without involving changes of the DNA sequence. […] The valuable information generated by various genomic, transcriptomic and epigenetic alterations provide us with a comprehensive assessment about how these changes may affect key signaling pathways supporting the development of HCC.

• #41 Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

  https://www.mdpi.com/2227-9059/10/12/3202

  Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. […] In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC.

• #42 Advances in the study of the mechanism of action of miR‑22 in liver lesions (Review)

  https://www.spandidos-publications.com/10.3892/ol.2024.14674

  Globally, nearly 2 million deaths annually are attributed to the development of liver diseases, with liver cancer and cirrhosis being particularly prominent, which makes liver disease a significant global health concern. […] Among them, miR22 serves a unique role in mediating multiple pathway mechanisms and epigenetic modifications and can act both as an inhibitor of liver cancer and a metabolic blocker. […] The present manuscript aimed to comprehensively review the key role of miR22 in the evolution of liver diseases and offer valuable references and guidance for subsequent studies by identifying its specific mechanism of action and future development prospects. […] With recent advancements in liver cancer research, the role of miR-22 as an inhibitor of liver cancer has received attention.

• #43 Advances in the study of the mechanism of action of miR‑22 in liver lesions (Review)

  https://www.spandidos-publications.com/10.3892/ol.2024.14674

  As a tumour suppressor, miR-22 regulates the expression of tumour-related factors via multiple pathways, which can inhibit liver cancer occurrence and development. […] The expression levels of miR-22 are significantly downregulated in HCC and show a gradual decrease with the continuous progression of cancer stages. […] Multiple mechanisms associated with miR-22 have been reported to be involved in the occurrence and development of liver cancer. […] Zhang et al (35) reported that miR-22 overexpression in HCC tissues significantly reduced histone deacetylase 4 (HDAC4) expression, thereby inhibiting the proliferation of Hep3B and SMMC7721 HCC cells. […] In HCC, MIR22HG functions as a competitive endogenous RNA (ceRNA), which regulates miRNA-10a-5p/nuclear receptor corepressor 2 to inhibit the Wnt/-catenin signalling pathway, thereby inhibiting the growth, invasion and migration of HCC cells.

• #44 Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics | Aging

  https://www.aging-us.com/article/203620

  Aging involves progressive physiological and metabolic reprogramming to adapt to gradual deterioration of organs and functions. This includes mechanisms of defense against pre-malignant transformations. Thus, certain tumors are more prone to appear in elderly patients. This is the case of the two most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). […] Aging hallmarks, such as genomic instability, telomere attrition, epigenetic alterations, altered proteostasis, mitochondrial dysfunction, cellular senescence, exhaustion of stem cell niches, impaired intracellular communication, and deregulated nutrient sensing can play an important role in liver carcinogenesis in the elders. […] Increased liver fragility determines a worse response to risk factors, which more frequently affect the aged population. This, together with the difficulty to carry out an early detection of HCC and iCCA, accounts for the late diagnosis of these tumors, which usually occurs in patients with approximately 60 and 70 years, respectively.

• #45 Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics | Aging

  https://www.aging-us.com/article/203620

  Aging involves progressive physiological and metabolic reprogramming to adapt to gradual deterioration of organs and functions. This includes mechanisms of defense against pre-malignant transformations. Thus, certain tumors are more prone to appear in elderly patients. This is the case of the two most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). […] Aging hallmarks, such as genomic instability, telomere attrition, epigenetic alterations, altered proteostasis, mitochondrial dysfunction, cellular senescence, exhaustion of stem cell niches, impaired intracellular communication, and deregulated nutrient sensing can play an important role in liver carcinogenesis in the elders. […] Increased liver fragility determines a worse response to risk factors, which more frequently affect the aged population. This, together with the difficulty to carry out an early detection of HCC and iCCA, accounts for the late diagnosis of these tumors, which usually occurs in patients with approximately 60 and 70 years, respectively.

• #46 Impact of aging on primary liver cancer: epidemiology, pathogenesis and therapeutics | Aging

  https://www.aging-us.com/article/203620

  Aging involves progressive physiological and metabolic reprogramming to adapt to gradual deterioration of organs and functions. This includes mechanisms of defense against pre-malignant transformations. Thus, certain tumors are more prone to appear in elderly patients. This is the case of the two most frequent types of primary liver cancer, i.e., hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). […] Aging hallmarks, such as genomic instability, telomere attrition, epigenetic alterations, altered proteostasis, mitochondrial dysfunction, cellular senescence, exhaustion of stem cell niches, impaired intracellular communication, and deregulated nutrient sensing can play an important role in liver carcinogenesis in the elders. […] Increased liver fragility determines a worse response to risk factors, which more frequently affect the aged population. This, together with the difficulty to carry out an early detection of HCC and iCCA, accounts for the late diagnosis of these tumors, which usually occurs in patients with approximately 60 and 70 years, respectively.

• #47 Encouraging normal liver cells to fight cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2019/11/191125120954.htm

  A study discovered that healthy liver tissue surrounding a tumor activates a defense mechanism that restrains tumor growth. […] Remarkably, the researchers found that hyperactivation of this mechanism above levels normally present in the liver, triggered the elimination of different types of liver tumors in mice. […] The study, led by Prof. Georg Halder (VIB-KU Leuven Center for Cancer Biology), showed that not only the immune system but also non-cancerous liver cells around liver tumors have the capacity to kill nearby tumor cells. […] Prof. Halder says: „While the study shows that this anti-tumor mechanism exists, how exactly activated liver cells cause the elimination of cancer cells is not known, but it is obviously a highly significant question that we are currently investigating.”

• #48 Encouraging normal liver cells to fight cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2019/11/191125120954.htm

  A study discovered that healthy liver tissue surrounding a tumor activates a defense mechanism that restrains tumor growth. […] Remarkably, the researchers found that hyperactivation of this mechanism above levels normally present in the liver, triggered the elimination of different types of liver tumors in mice. […] The study, led by Prof. Georg Halder (VIB-KU Leuven Center for Cancer Biology), showed that not only the immune system but also non-cancerous liver cells around liver tumors have the capacity to kill nearby tumor cells. […] Prof. Halder says: „While the study shows that this anti-tumor mechanism exists, how exactly activated liver cells cause the elimination of cancer cells is not known, but it is obviously a highly significant question that we are currently investigating.”

• #49 Encouraging normal liver cells to fight cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2019/11/191125120954.htm

  By studying tumor tissues from cancer patients and mouse models for liver cancer, the scientists found that the genes YAP and TAZ were activated around tumors in the liver and that this was the driving force of the anti-tumor mechanism. […] „The identification of anti-tumor functions in genes traditionally considered as tumor promoting genes completely changes how we think about cancer genes and their function in normal tissues,” says Ivn Moya, first author of the paper. […] „Given the striking anti-tumor effect of YAP-activated liver cells on liver tumors, our discovery has the potential to provide ground-breaking insights into a novel strategy to fight,” says Stephanie Castaldo, co-first-author. […] „Indeed, the next step is to test to what degree this mechanism also affects human cancer cells,” says Laura Van den Mooter, also co-first-author.

• #50 Encouraging normal liver cells to fight cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2019/11/191125120954.htm

  A study discovered that healthy liver tissue surrounding a tumor activates a defense mechanism that restrains tumor growth. […] Remarkably, the researchers found that hyperactivation of this mechanism above levels normally present in the liver, triggered the elimination of different types of liver tumors in mice. […] The study, led by Prof. Georg Halder (VIB-KU Leuven Center for Cancer Biology), showed that not only the immune system but also non-cancerous liver cells around liver tumors have the capacity to kill nearby tumor cells. […] Prof. Halder says: „While the study shows that this anti-tumor mechanism exists, how exactly activated liver cells cause the elimination of cancer cells is not known, but it is obviously a highly significant question that we are currently investigating.”

• #51 Hepatocellular carcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-00240-3

  Liver cancer remains a global health challenge, with an estimated incidence of 1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. […] Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. […] The current major advancements have impacted the management of patients with advanced HCC. […] New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.

• #52

  https://link.springer.com/article/10.1186/s43556-024-00184-0

  Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. […] Despite numerous studies on the mechanisms underlying liver cancer, tyrosine kinase inhibitors (TKIs) are the only widely used clinical inhibitors, represented by sorafenib, whose clinical application is greatly limited by the phenomenon of drug resistance. […] Here we show an in-depth discussion of the signaling pathways frequently implicated in liver cancer pathogenesis and the inhibitors targeting these pathways under investigation or already in use in the management of advanced liver cancer. […] Given that TKIs represent the sole class of targeted therapeutics for liver cancer employed in clinical practice, we have particularly focused on TKIs and the mechanisms of the commonly encountered phenomena of its resistance during HCC treatment.

• #53 Hepatocellular carcinoma | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-020-00240-3

  Liver cancer remains a global health challenge, with an estimated incidence of 1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. […] Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. […] The current major advancements have impacted the management of patients with advanced HCC. […] New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.

• #54

  https://link.springer.com/article/10.1186/s43556-024-00184-0

  From an overarching perspective, the tumor microenvironment (TME) of HCC comprising cancer cells, immune cells, cytokines, and the extracellular matrix is crucial in facilitating signaling pathways that promote tumors and aid in developing resistance to treatment. […] Therefore, investigating the molecular basis of the pathogenesis of liver cancer, especially HCC, and identifying potential therapeutic targets is crucial for developing interventions or effective treatment strategies, enhancing the prognosis of patients. […] Given the complexity of HCC pathogenesis, targeted therapy remains immature and the application is highly limited despite numerous studies underway. […] This review aims to collate information on pro-tumor pathways of liver cancer and the progression of pathway-specific inhibitors, thereby offering insights for the future development of targeted therapies. […] Overall, this review highlights potential avenues for future advancements in the targeted therapy of liver cancer.

• #55 Mechanism used by metastatic cancer cells to infiltrate the liver found | ScienceDaily

  https://www.sciencedaily.com/releases/2022/10/221004104959.htm

  However, new tumors could be prevented from forming by treating the mice with a MMP9 inhibitor, suggesting that MMP9 is a promising therapeutic target to prevent liver metastasis. […] Professor Matsubara concluded, „In this study, we discovered a new phenomenon related to metastasis: cancer cells induce LSEC intracellular gap formation and infiltrate the liver through those gaps.”

• #56

  https://resou.osaka-u.ac.jp/en/research/2023/20230704_1

  Subsequent analysis revealed the pathway by which GREB1 activation leads to the development of cancer. […] We have now shown that a protein called HNF4 changes its function when cooperating with GREB1, explains first author Shinji Matsumoto. This leads to tumor promotion when Wnt signaling is abnormally activated. […] Therefore, GREB1 is responsible for integrating the conflicting cellular states of differentiation and proliferation. […] The team went on to look at large-scale cancer datasets publicly available online and could see that GREB1 expression and Wnt signaling activation were correlated in liver cancer samples. […] They also demonstrated that inhibition of GREB1 expression, using a technology known as antisense oligonucleotides (small nucleic acid molecules that inhibit a specific gene), showed anti-cancer effects. […] This highly significant study widens our knowledge of how gene expression alters as cancer develops and reveals the potential for new therapies for liver cancer in the future.

• #57 Molecular mechanism of cinobufotalin against liver cancer | DDDT

  https://www.dovepress.com/validation-of-core-ingredients-and-molecular-mechanism-of-cinobufotali-peer-reviewed-fulltext-article-DDDT

  It was found that cinobufotalin injection exerts anti-tumor therapeutic effects on liver cancer by blocking cell cycle progression in a manner dependent on the core targets, which provides scientific evidence for the clinical application of cinobufotalin injection and the development of novel anti-liver cancer drugs.

• #58 Molecular Pathogenesis of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5075835/

  In HCC, a recent comprehensive study provided insight on the origin of liver CSCs. […] Over the past decade, a number of liver CSC surface markers have been identified, as evidenced by the functional CSC properties. […] Dysregulation of these two pathways has also been found to be associated with the maintenance of liver CSCs. […] The linkage between NF-B and liver CSCs appears to be a promising area of study. […] Despite the emergence of various therapeutic modalities including chemotherapy, targeted therapy and radiotherapy in recent years, the efficacy in eradicating HCC is still unsatisfactory partially attributed to resistance to treatment conferred by liver CSCs. […] Identification of key molecular events and crucial signaling pathways provides insight to devise targeted therapies to treat this cancer.

• #59 Hepatocellular carcinoma pathogenesis: from genes to environment | Nature Reviews Cancer

  https://www.nature.com/articles/nrc1934

  Genomic instability is a common feature of human HCC. Various mechanisms are thought to contribute, including telomere erosion, chromosome segregation defects and alterations in the DNA-damage-response pathways. […] There are many genomic alterations in HCC. Comparative genomic hybridization studies so far have pointed to frequent chromosomal gains in 1q, 6p, 8q, 11q and 17q, and losses in 1p, 4q, 8p, 13q and 17p. […] Gene-expression analyses of human HCCs have led to the successful molecular classification of HCCs on the basis of prognosis, aetiology and intrahepatic recurrence. […] Many challenges and opportunities exist in this field, including the need for a more detailed and clinically grounded genomic characterization of human HCCs, deeper understanding of the mechanisms of genomic instability, host-viral interactions, microenvironmental processes (inflammation and cirrhosis), cell of origin in hepatocarcinogenesis and the identification of biomarkers to identify early stage disease as well as those at greatest risk of developing HCC.

Zobacz więcej