Materiały źródłowe

• #1 Non-Melanoma Skin Cancers: Biological and Clinical Features

  https://ouci.dntb.gov.ua/en/works/4bxX5Va9/

  Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Merkel cell carcinoma (MCC). […] While the deregulation of the Hedgehog pathway is commonly observed in BCC, SCC and MCC are characterized by a strikingly elevated mutational and neoantigen burden. […] Herein, we review the most relevant biological and clinical features of NMSC, focusing on innovative treatment approaches. […] In spite of considerable progress, our understanding of the mechanisms that control NMSC development and their associated molecular and immunological landscapes is still limited. […] Here we demonstrated a critical role for galectin-7 (Gal-7), a β-galactoside-binding protein preferentially expressed in skin tissue, during NMSC development. […] Thus, Gal-7 emerges as a critical mediator of skin carcinogenesis and a potential therapeutic target in human NMSC.

• #2 What Are Basal and Squamous Cell Skin Cancers? | Types of Skin Cancer | American Cancer Society

  https://www.cancer.org/cancer/types/basal-and-squamous-cell-skin-cancer/about/what-is-basal-and-squamous-cell.html

  Basal and squamous cell skin cancers are the most common types of skin cancer. These cancers are often related to sun exposure. […] Most skin cancers start in the top layer of skin, called the epidermis. […] When these cells grow out of control, they can develop into squamous cell skin cancer (also called squamous cell carcinoma). […] Skin cancers that start in the basal cell layer are called basal cell skin cancers or basal cell carcinomas. […] The epidermis is separated from the deeper layers of skin (the dermis and the subcutis) by a thin layer of tissue known as the basement membrane. When a skin cancer becomes more advanced, it generally grows through this barrier and into the deeper layers. […] Basal cell carcinoma (BCC, also called basal cell skin cancer, or just basal cell cancer) is most common type of skin cancer. About 8 out of 10 skin cancers are basal cell carcinomas.

• #3 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  (1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; […] (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; […] (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development.

• #4 What Are Basal and Squamous Cell Skin Cancers? | Types of Skin Cancer | American Cancer Society

  https://www.cancer.org/cancer/types/basal-and-squamous-cell-skin-cancer/about/what-is-basal-and-squamous-cell.html

  These cancers start in the basal cell layer, which is the lower part of the epidermis. […] If BCC is left untreated, it can grow into nearby areas and invade the bone or other tissues beneath the skin. […] About 2 out of 10 skin cancers are squamous cell carcinomas (SCCs, also called squamous cell skin cancers, cutaneous squamous cell cancers, or just squamous cell cancers). These cancers start in the flat cells in the upper (outer) part of the epidermis. […] Squamous cell cancers can usually be removed completely (or treated in other ways), although they are much more likely than basal cell cancers to grow into deeper layers of skin and spread to other parts of the body. […] Actinic keratosis (AK), also known as solar keratosis, is a pre-cancerous skin condition caused by too much exposure to the sun.

• #5 Basal-cell carcinoma – Wikipedia

  https://en.wikipedia.org/wiki/Basal-cell_carcinoma

  Basal-cell carcinoma is named after the basal cells that populate the lowest layer of the epidermis due to the histological appearance of the cancer cells under the microscope. Nevertheless, not all basal-cell carcinomas actually originate within the basal layer. Basal-cell carcinomas are thought to develop from the folliculosebaceousapocrine germinative cells known as trichoblasts. […] Overexposure to the sun leads to the formation of thymine dimers, a form of DNA damage. While DNA repair removes most UV-induced damage, not all crosslinks are excised. There is, therefore, cumulative DNA damage leading to mutations. Apart from the mutagenesis, overexposure to sunlight depresses the local immune system, possibly decreasing immune surveillance for new tumor cells. Studies of the role of DNA repair in susceptibility to sunlight-induced basal cell carcinoma indicated that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.

• #6 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The primary risk factor for cutaneous carcinogenesis is cumulative UV exposure from sunlight and/or tanning beds, which lead to UV-induced alteration in skin protein expression. UV exposure is considered as a complete carcinogen, since it affects each stage of carcinogenesis. In fact, it leads to cellular damage because of the reduction of cell-mediated immune responses, production of reactive oxygen species (ROS) and DNA alteration. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. Indeed, UVB-induced carcinogenesis amplifies the risk of developing BCC in immunosuppressed patients and in people with Fitzpatrick skin types I and II. […] It has been reported that UV irradiation of keratinocytes enhances the pro-opiomelanocortin gene (POMC) and α-melanocyte-stimulating hormone (αMSH) production, which are critically involved in determining whether the skin produces brown-black pigment (eumelanin) or red-yellow pigment (pheomelanin).

• #7 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The primary risk factor for cutaneous carcinogenesis is cumulative UV exposure from sunlight and/or tanning beds, which lead to UV-induced alteration in skin protein expression. UV exposure is considered as a complete carcinogen, since it affects each stage of carcinogenesis. In fact, it leads to cellular damage because of the reduction of cell-mediated immune responses, production of reactive oxygen species (ROS) and DNA alteration. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. Indeed, UVB-induced carcinogenesis amplifies the risk of developing BCC in immunosuppressed patients and in people with Fitzpatrick skin types I and II. […] It has been reported that UV irradiation of keratinocytes enhances the pro-opiomelanocortin gene (POMC) and α-melanocyte-stimulating hormone (αMSH) production, which are critically involved in determining whether the skin produces brown-black pigment (eumelanin) or red-yellow pigment (pheomelanin).

• #8 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The primary risk factor for cutaneous carcinogenesis is cumulative UV exposure from sunlight and/or tanning beds, which lead to UV-induced alteration in skin protein expression. UV exposure is considered as a complete carcinogen, since it affects each stage of carcinogenesis. In fact, it leads to cellular damage because of the reduction of cell-mediated immune responses, production of reactive oxygen species (ROS) and DNA alteration. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. Indeed, UVB-induced carcinogenesis amplifies the risk of developing BCC in immunosuppressed patients and in people with Fitzpatrick skin types I and II. […] It has been reported that UV irradiation of keratinocytes enhances the pro-opiomelanocortin gene (POMC) and α-melanocyte-stimulating hormone (αMSH) production, which are critically involved in determining whether the skin produces brown-black pigment (eumelanin) or red-yellow pigment (pheomelanin).

• #9 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The primary risk factor for cutaneous carcinogenesis is cumulative UV exposure from sunlight and/or tanning beds, which lead to UV-induced alteration in skin protein expression. UV exposure is considered as a complete carcinogen, since it affects each stage of carcinogenesis. In fact, it leads to cellular damage because of the reduction of cell-mediated immune responses, production of reactive oxygen species (ROS) and DNA alteration. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. Indeed, UVB-induced carcinogenesis amplifies the risk of developing BCC in immunosuppressed patients and in people with Fitzpatrick skin types I and II. […] It has been reported that UV irradiation of keratinocytes enhances the pro-opiomelanocortin gene (POMC) and α-melanocyte-stimulating hormone (αMSH) production, which are critically involved in determining whether the skin produces brown-black pigment (eumelanin) or red-yellow pigment (pheomelanin).

• #10 Disease Management: Nonmelanoma Skin Cancer

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/nonmelanoma-skin-cancer/

  The etiology of NMSC is strongly tied to ultraviolet (UV) radiation. […] The most common causative factor of BCC is UV radiation. UVB radiation has been shown to induce characteristic DNA mutations in keratinocytes called dipyrimidine dimers and manifest as signature mutations in tumor protein 53 (TP53), an important tumor suppressor gene. […] Although the exact mechanism of BCC propagation remains unclear, it is believed to arise when mutations that control cell growth activate pluripotential stem cells in the epidermis. […] Cumulative UV exposure is the primary etiological factor for SCC in fair-skinned individuals. […] As in the pathogenesis of BCC, UV radiation leads to the formation of dipyrimidine dimers and mutagenesis of the p53 tumor-suppressor gene. A nonfunctional p53 protein leads to dysregulation of the cell cycle, uncontrolled growth and proliferation of aberrant keratinocytes.

• #11 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The primary risk factor for cutaneous carcinogenesis is cumulative UV exposure from sunlight and/or tanning beds, which lead to UV-induced alteration in skin protein expression. UV exposure is considered as a complete carcinogen, since it affects each stage of carcinogenesis. In fact, it leads to cellular damage because of the reduction of cell-mediated immune responses, production of reactive oxygen species (ROS) and DNA alteration. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. Indeed, UVB-induced carcinogenesis amplifies the risk of developing BCC in immunosuppressed patients and in people with Fitzpatrick skin types I and II. […] It has been reported that UV irradiation of keratinocytes enhances the pro-opiomelanocortin gene (POMC) and α-melanocyte-stimulating hormone (αMSH) production, which are critically involved in determining whether the skin produces brown-black pigment (eumelanin) or red-yellow pigment (pheomelanin).

• #12 Disease Management: Nonmelanoma Skin Cancer

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/nonmelanoma-skin-cancer/

  The etiology of NMSC is strongly tied to ultraviolet (UV) radiation. […] The most common causative factor of BCC is UV radiation. UVB radiation has been shown to induce characteristic DNA mutations in keratinocytes called dipyrimidine dimers and manifest as signature mutations in tumor protein 53 (TP53), an important tumor suppressor gene. […] Although the exact mechanism of BCC propagation remains unclear, it is believed to arise when mutations that control cell growth activate pluripotential stem cells in the epidermis. […] Cumulative UV exposure is the primary etiological factor for SCC in fair-skinned individuals. […] As in the pathogenesis of BCC, UV radiation leads to the formation of dipyrimidine dimers and mutagenesis of the p53 tumor-suppressor gene. A nonfunctional p53 protein leads to dysregulation of the cell cycle, uncontrolled growth and proliferation of aberrant keratinocytes.

• #13 Risk factors for non-melanoma skin cancer | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/skin-non-melanoma/risks

  SCC is most strongly linked to total lifetime sun exposure. This includes recreational and work-related exposure and being exposed to UVR a lot during childhood. […] People with fair or light-coloured skin have a higher risk of developing non-melanoma skin cancer than people with other skin types. […] People who have already had skin cancer (non-melanoma or melanoma) have a greater risk of developing another skin cancer, including BCC and SCC. […] People who had radiation therapy (a source of ionizing radiation) have a greater risk of developing non-melanoma skin cancer in the treatment area. This type of skin cancer can develop 15 to 20 years after they received radiation therapy. […] Coming into contact with arsenic increases the risk of developing non-melanoma skin cancer. […] Working with certain products increases the risk of developing non-melanoma skin cancer.

• #14 Skin cancer – Wikipedia

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

  Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. It occurs when skin cells grow uncontrollably, forming malignant tumors. The primary cause of skin cancer is prolonged exposure to ultraviolet (UV) radiation from the sun or tanning devices. More than 90% of cases are caused by exposure to ultraviolet radiation from the Sun. This exposure increases the risk of all three main types of skin cancer. BCC and SCC often carry a UV-signature mutation indicating that these cancers are caused by UVB radiation via direct DNA damage. However, malignant melanoma is predominantly caused by UVA radiation via indirect DNA damage. The indirect DNA damage is caused by free radicals and reactive oxygen species. A molecular factor involved in the disease process is mutation in gene PTCH1 that plays an important role in the Sonic hedgehog signaling pathway.

• #15 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Genetic factors play a crucial role in the development of cancer and specific mechanisms, genes, and tumor microenvironment features are involved. […] This review aims to update the genetic aspects that trigger NMSC, propose new candidate genes, and establish the relevance of the interacting cells and molecules in the tumor microenvironment. […] DNA damage caused by UVR and its intensity is the principal hallmark of skin carcinomas. […] Consistent with this, it can be estimated that one hour of exposure can generate 100,000 to 200,000 DNA lesions, affecting replication and transcription processes if they are not properly repaired. […] Indeed, recent studies identified that NMSC lesions can acquire mutations that cause phenotypic changes towards more aggressive types. […] This plasticity of cancer cells allows them to escape from cellular regulation mechanisms.

• #16 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Repair mechanisms for DNA damage, such as DNA photolyase to remove covalent bonds between adjacent pyrimidines and nucleotide excision repair (NER) for cyclobutane pyrimidine dimers as a consequence of UVB radiation, are well-known. […] Candidate genes for UV response have been proposed. […] Environmental risk factors are well-known, and aging must be considered a personal risk factor for each individual, which can potentiate the effect of radiation exposure. […] Several genes and molecular mechanisms have been described to date. […] Alterations in the functioning of essential signaling pathways in cell growth control continue to drive carcinogenesis processes. […] Sonic Hedgehog signaling, a highly conserved developmental pathway in organogenesis from embryonic stages, and its role in tissue maintenance, regeneration, and repair, has been recognized for decades.

• #17 Apoptosis and Pathogenesis of Melanoma and Nonmelanoma Skin Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-0-387-77574-6_22

  Skin cancers, i.e., basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, belong to the most frequent tumors. Their formation is based on constitutional and/or inherited factors usually combined with environmental factors, mainly UV-irradiation through long term sun exposure. […] UV-light can randomly induce DNA damage in keratinocytes, but it can also mutate genes essential for control and surveillance in the skin epidermis. Various repair and safety mechanisms exist to maintain the integrity of the skin epidermis. For example, UV-light damaged DNA is repaired and if this is not possible, the DNA damaged cells are eliminated by apoptosis (sunburn cells). This occurs under the control of the p53 suppressor gene. […] Mutation in the p53 gene is the starting point for the formation of SCC and some forms of BCC. Other BCCs originate through UV light mediated mutations of genes of the hedgehog signaling pathway which are essential for the maintainance of cell growth and differentiation. The transcription factor Gli2 plays a key role within this pathway, indeed, Gli2 is responsible for the marked apoptosis resistance of the BCCs.

• #18 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  Therefore, heparanase is involved in BCC and SCC formation. […] In addition, UV exposure affects the p53 expression, which is altered in both AKs and SCC. […] X-rays play a role in the pathogenesis of NMSC. […] It has been reported that several class I and class II HLA allele groups were associated with SCC in immunosuppressed patients, including HLA-B*27, HLA-A*03 and HLA-DQA1*01. […] Immunosuppression also plays a role in carcinogenesis, leading to an easier NMSC development. […] The risk of developing SCC is also increased by exposure to carcinogenic chemicals, above all arsenic. […] The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy. […] Non-melanoma skin cancers (NMSCs) are the most common malignancy worldwide, of which 99% are basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of skin.

• #19 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  Therefore, heparanase is involved in BCC and SCC formation. […] In addition, UV exposure affects the p53 expression, which is altered in both AKs and SCC. […] X-rays play a role in the pathogenesis of NMSC. […] It has been reported that several class I and class II HLA allele groups were associated with SCC in immunosuppressed patients, including HLA-B*27, HLA-A*03 and HLA-DQA1*01. […] Immunosuppression also plays a role in carcinogenesis, leading to an easier NMSC development. […] The risk of developing SCC is also increased by exposure to carcinogenic chemicals, above all arsenic. […] The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy. […] Non-melanoma skin cancers (NMSCs) are the most common malignancy worldwide, of which 99% are basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of skin.

• #20 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  It has also been reported that mast cells (MCs) in skin show an increase in response to UV radiation because of IL-33 production from keratinocytes and dermal fibroblasts. […] It has been suggested that exposure to chronic UVB radiation determines heparanase activation, which causes the degradation of heparin sulfate and increments the interaction between the epidermal growth factor and the dermis. […] Therefore, heparanase is involved in BCC and SCC formation. […] In addition, UV exposure affects the p53 expression, which is altered in both AKs and SCC. Therefore, this mutation could further confirm that AK is an invasive SCC (iSCC) precursor. […] Cutaneous HPV is classified into alpha, beta and gamma types. Beta-HPV is thought to be a cofactor in SCC pathogenesis in immunosuppressed patients.

• #21 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The risk of developing SCC is also increased by exposure to carcinogenic chemicals, above all arsenic. […] Immunosuppression also plays a role in carcinogenesis, leading to an easier NMSC development. […] The heterogeneous expression of class I HLA proteins in SCC may also explain why immunosuppression increases the SCC risk 65-fold, but BCC risk only 10-fold. […] Therefore, Yesantharao et al. proposed that the abnormal expression of the HLA-G protein on the surface of SCC cancer cells in immunosuppressed patients allowed for the evasion of immune surveillance. […] The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy. […] Although skin carcinogenesis is still not fully understood, several papers have demonstrated the presence of genetic and molecular alterations involved in this process.

• #22 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The risk of developing SCC is also increased by exposure to carcinogenic chemicals, above all arsenic. […] Immunosuppression also plays a role in carcinogenesis, leading to an easier NMSC development. […] The heterogeneous expression of class I HLA proteins in SCC may also explain why immunosuppression increases the SCC risk 65-fold, but BCC risk only 10-fold. […] Therefore, Yesantharao et al. proposed that the abnormal expression of the HLA-G protein on the surface of SCC cancer cells in immunosuppressed patients allowed for the evasion of immune surveillance. […] The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy. […] Although skin carcinogenesis is still not fully understood, several papers have demonstrated the presence of genetic and molecular alterations involved in this process.

• #23 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  Therefore, heparanase is involved in BCC and SCC formation. […] In addition, UV exposure affects the p53 expression, which is altered in both AKs and SCC. […] X-rays play a role in the pathogenesis of NMSC. […] It has been reported that several class I and class II HLA allele groups were associated with SCC in immunosuppressed patients, including HLA-B*27, HLA-A*03 and HLA-DQA1*01. […] Immunosuppression also plays a role in carcinogenesis, leading to an easier NMSC development. […] The risk of developing SCC is also increased by exposure to carcinogenic chemicals, above all arsenic. […] The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy. […] Non-melanoma skin cancers (NMSCs) are the most common malignancy worldwide, of which 99% are basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of skin.

• #24 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  Therefore, heparanase is involved in BCC and SCC formation. […] In addition, UV exposure affects the p53 expression, which is altered in both AKs and SCC. […] X-rays play a role in the pathogenesis of NMSC. […] It has been reported that several class I and class II HLA allele groups were associated with SCC in immunosuppressed patients, including HLA-B*27, HLA-A*03 and HLA-DQA1*01. […] Immunosuppression also plays a role in carcinogenesis, leading to an easier NMSC development. […] The risk of developing SCC is also increased by exposure to carcinogenic chemicals, above all arsenic. […] The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy. […] Non-melanoma skin cancers (NMSCs) are the most common malignancy worldwide, of which 99% are basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of skin.

• #25 Risk factors for non-melanoma skin cancer | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/skin-non-melanoma/risks

  PUVA therapy is a treatment used for skin conditions such as psoriasis. It uses the drug psoralen and UVA radiation. Psoralen makes the skin more sensitive to UVA light. Receiving PUVA therapy for a long time increases your risk of developing SCC. […] Xeroderma pigmentosum is a hereditary condition that affects the skin so it cant repair sun damage. […] People with a weakened immune system have a higher risk of developing non-melanoma skin cancer.

• #26 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Repair mechanisms for DNA damage, such as DNA photolyase to remove covalent bonds between adjacent pyrimidines and nucleotide excision repair (NER) for cyclobutane pyrimidine dimers as a consequence of UVB radiation, are well-known. […] Candidate genes for UV response have been proposed. […] Environmental risk factors are well-known, and aging must be considered a personal risk factor for each individual, which can potentiate the effect of radiation exposure. […] Several genes and molecular mechanisms have been described to date. […] Alterations in the functioning of essential signaling pathways in cell growth control continue to drive carcinogenesis processes. […] Sonic Hedgehog signaling, a highly conserved developmental pathway in organogenesis from embryonic stages, and its role in tissue maintenance, regeneration, and repair, has been recognized for decades.

• #27 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Verkouteren et al. described that about 85% of sporadic BCC could display variants in genes implicated in Hedgehog signaling (SHH, SMO, GLI1, GLI2, GL3), in which loss of heterozygosity (LOH) is a common trait, although the profile of genetic variants in BCC is complex and variable. […] Additionally, a disrupted function of TP53 gene has been established as the second most frequent cause of BCC, because of the lack of cell cycle arrest over DNA damage. […] Through coding and non-coding somatic variant analysis in this type of NMSC in 191 patients, mutations in PTCH1 and TP53 genes were found in 58.6% and 31.4% of the cases, whereas variants in TERT and DPH3 promoters were detected in 59.2% and 38.2%, respectively. […] In contrast, a study cohort with a smaller sample of patients with sporadic BCC found PTCH1 mutations in 72% of the cases, along with other genes such as CSMD1 (63%), TERT promoter (58%), DPH3 promoter (49%), TP53 (46%), NOTCH1 (44%), DPP10 (35%) representing the wide variability and cellular mechanisms involved in BCC pathogenesis.

• #28 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Verkouteren et al. described that about 85% of sporadic BCC could display variants in genes implicated in Hedgehog signaling (SHH, SMO, GLI1, GLI2, GL3), in which loss of heterozygosity (LOH) is a common trait, although the profile of genetic variants in BCC is complex and variable. […] Additionally, a disrupted function of TP53 gene has been established as the second most frequent cause of BCC, because of the lack of cell cycle arrest over DNA damage. […] Through coding and non-coding somatic variant analysis in this type of NMSC in 191 patients, mutations in PTCH1 and TP53 genes were found in 58.6% and 31.4% of the cases, whereas variants in TERT and DPH3 promoters were detected in 59.2% and 38.2%, respectively. […] In contrast, a study cohort with a smaller sample of patients with sporadic BCC found PTCH1 mutations in 72% of the cases, along with other genes such as CSMD1 (63%), TERT promoter (58%), DPH3 promoter (49%), TP53 (46%), NOTCH1 (44%), DPP10 (35%) representing the wide variability and cellular mechanisms involved in BCC pathogenesis.

• #29 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Verkouteren et al. described that about 85% of sporadic BCC could display variants in genes implicated in Hedgehog signaling (SHH, SMO, GLI1, GLI2, GL3), in which loss of heterozygosity (LOH) is a common trait, although the profile of genetic variants in BCC is complex and variable. […] Additionally, a disrupted function of TP53 gene has been established as the second most frequent cause of BCC, because of the lack of cell cycle arrest over DNA damage. […] Through coding and non-coding somatic variant analysis in this type of NMSC in 191 patients, mutations in PTCH1 and TP53 genes were found in 58.6% and 31.4% of the cases, whereas variants in TERT and DPH3 promoters were detected in 59.2% and 38.2%, respectively. […] In contrast, a study cohort with a smaller sample of patients with sporadic BCC found PTCH1 mutations in 72% of the cases, along with other genes such as CSMD1 (63%), TERT promoter (58%), DPH3 promoter (49%), TP53 (46%), NOTCH1 (44%), DPP10 (35%) representing the wide variability and cellular mechanisms involved in BCC pathogenesis.

• #30 Basal Cell Carcinoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/276624-overview

  Zhang et al reported that ultraviolet (UV)-specific nucleotide changes in PTCH, as well as the tumor suppressor gene TP53, are implicated in the development of early-onset BCC. […] UV-induced mutations in the TP53 tumor suppressor gene, which resides on band 17p13.1, have been found in some cases of BCC. […] Radiation has proven to be tumorigenic by two mechanisms. The first entails the initiations of prolonged cellular proliferation, thereby increasing the likelihood of transcription errors that can lead to cellular transformation. The second mechanism is direct damage of DNA replication, leading to cellular mutation that may activate proto-oncogenes or deactivate tumor suppressor genes. […] Immunologically, the mechanism by which prolonged ultraviolet radiation exposure leads to the development of BCC includes suppression of the cutaneous immune system and immunologic unresponsiveness to cutaneous tumors.

• #31 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Regarding SCC, earlier reports about TP53 determined the role of this tumor suppressor gene in skin carcinogenesis mediated by UVB radiation, observing that exposed knockout mice developed this type of NMSC. […] Recently, studies with whole-exome sequencing (WES) described the prevalence of oncogenic variants on this gene in 60% of the analyzed samples, in contrast to the adjacent UV-exposed epidermis. […] The immune system and its regulation are essential in NMSC emergence and tumor microenvironment establishment. […] Indeed, UVB radiation also has an impact on the immune response, which can induce immunosuppression, such as a reduction in Langerhans cell (from the skin immune system) antigen-presenting capacity, due to apoptosis and lymph node migration. […] The combination of UVB-induced ROS, DNA damage, cytokines, and chemokines release affects epidermal cells’ stability.

• #32 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Regarding SCC, earlier reports about TP53 determined the role of this tumor suppressor gene in skin carcinogenesis mediated by UVB radiation, observing that exposed knockout mice developed this type of NMSC. […] Recently, studies with whole-exome sequencing (WES) described the prevalence of oncogenic variants on this gene in 60% of the analyzed samples, in contrast to the adjacent UV-exposed epidermis. […] The immune system and its regulation are essential in NMSC emergence and tumor microenvironment establishment. […] Indeed, UVB radiation also has an impact on the immune response, which can induce immunosuppression, such as a reduction in Langerhans cell (from the skin immune system) antigen-presenting capacity, due to apoptosis and lymph node migration. […] The combination of UVB-induced ROS, DNA damage, cytokines, and chemokines release affects epidermal cells’ stability.

• #33 Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/es-resistance-nonmelanoma-skin-cancer-nonsurgical-articulo-S1578219016302219

  Resistance is generally thought to be due to intrinsic factors inherent to the tumor cells or extrinsic factors in the tumor environment, which has an important role in treatment response through the establishment of gradients in factors such as signaling, O2, and metabolites. […] Intrinsic resistance may be due to a complex set of factors, including aspects related to the expression of genes involved in the genesis of NMSC and other aspects related to the photodynamic process itself. […] UV light-induced DNA mutations in tumor suppressor genes, such as p53, are common and have been described as early events in the carcinogenesis of 50% of BCCs and AKs and in 90% of SCCs. […] The oxidative stress caused by PDT activates signaling cascades involved in survival, proliferation, and inhibition of apoptosis mediated by protein kinase B (PKB/Akt), nuclear factor k (NF-kB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and cyclooxygenase-2 (COX-2), as well as genes involved in the antioxidant response pathway, such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) gene.

• #34 Disease Management: Nonmelanoma Skin Cancer

  https://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/dermatology/nonmelanoma-skin-cancer/

  The etiology of NMSC is strongly tied to ultraviolet (UV) radiation. […] The most common causative factor of BCC is UV radiation. UVB radiation has been shown to induce characteristic DNA mutations in keratinocytes called dipyrimidine dimers and manifest as signature mutations in tumor protein 53 (TP53), an important tumor suppressor gene. […] Although the exact mechanism of BCC propagation remains unclear, it is believed to arise when mutations that control cell growth activate pluripotential stem cells in the epidermis. […] Cumulative UV exposure is the primary etiological factor for SCC in fair-skinned individuals. […] As in the pathogenesis of BCC, UV radiation leads to the formation of dipyrimidine dimers and mutagenesis of the p53 tumor-suppressor gene. A nonfunctional p53 protein leads to dysregulation of the cell cycle, uncontrolled growth and proliferation of aberrant keratinocytes.

• #35 Advances in Skin Cancer | IntechOpen

  https://www.intechopen.com/chapters/1177229

  Recent studies have shown that UVR-induced signal transduction plays a huge role in the initiation and progression of non-melanoma cancer and is remarkably complex. […] Common mutations found in cSCC include those in RAS oncogene, which encodes RAS protein. This gene plays a crucial role in the evolution of non-melanoma carcinomas through regulation of proliferation, apoptosis, and angiogenesis. […] BCC originates from pluripotent interfollicular stem cells and involves mainly a mutation in the sonic Hedgehog signaling pathway as a result of high exposure to UV radiation in 90% of the cases. […] Another common affected pathway in BCC is found on the Canonical (-catenin dependent) Wingless (WNT) signaling pathway.

• #36 Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2017.5817

  Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. […] The fact that NMSC arises mostly on sun-exposed areas has highlighted the crucial role of UVR in the pathogenesis of NMSC. […] The immunosuppressive-inducing effects of UVR are primarily cited as conditioning a permissive tumor microenvironment for BCC and SCC. […] Various studies have suggested a link between neuroendocrine factors and skin carcinogenesis in the two most common types of NMSC, BCC and SCC. […] The mechanisms through which neuroendocrine factors influence mucocutaneous physiopathological processes are extremely complex, involving the dysregulation of the dynamic balance between the nervous, endocrine and immune systems.

• #37 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Regarding SCC, earlier reports about TP53 determined the role of this tumor suppressor gene in skin carcinogenesis mediated by UVB radiation, observing that exposed knockout mice developed this type of NMSC. […] Recently, studies with whole-exome sequencing (WES) described the prevalence of oncogenic variants on this gene in 60% of the analyzed samples, in contrast to the adjacent UV-exposed epidermis. […] The immune system and its regulation are essential in NMSC emergence and tumor microenvironment establishment. […] Indeed, UVB radiation also has an impact on the immune response, which can induce immunosuppression, such as a reduction in Langerhans cell (from the skin immune system) antigen-presenting capacity, due to apoptosis and lymph node migration. […] The combination of UVB-induced ROS, DNA damage, cytokines, and chemokines release affects epidermal cells’ stability.

• #38 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  The primary risk factor for cutaneous carcinogenesis is cumulative UV exposure from sunlight and/or tanning beds, which lead to UV-induced alteration in skin protein expression. UV exposure is considered as a complete carcinogen, since it affects each stage of carcinogenesis. In fact, it leads to cellular damage because of the reduction of cell-mediated immune responses, production of reactive oxygen species (ROS) and DNA alteration. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. Indeed, UVB-induced carcinogenesis amplifies the risk of developing BCC in immunosuppressed patients and in people with Fitzpatrick skin types I and II. […] It has been reported that UV irradiation of keratinocytes enhances the pro-opiomelanocortin gene (POMC) and α-melanocyte-stimulating hormone (αMSH) production, which are critically involved in determining whether the skin produces brown-black pigment (eumelanin) or red-yellow pigment (pheomelanin).

• #39 Non Melanoma Skin Cancer Pathogenesis Overview

  https://www.mdpi.com/2227-9059/6/1/6

  It has also been reported that mast cells (MCs) in skin show an increase in response to UV radiation because of IL-33 production from keratinocytes and dermal fibroblasts. […] It has been suggested that exposure to chronic UVB radiation determines heparanase activation, which causes the degradation of heparin sulfate and increments the interaction between the epidermal growth factor and the dermis. […] Therefore, heparanase is involved in BCC and SCC formation. […] In addition, UV exposure affects the p53 expression, which is altered in both AKs and SCC. Therefore, this mutation could further confirm that AK is an invasive SCC (iSCC) precursor. […] Cutaneous HPV is classified into alpha, beta and gamma types. Beta-HPV is thought to be a cofactor in SCC pathogenesis in immunosuppressed patients.

• #40 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  Regarding SCC, earlier reports about TP53 determined the role of this tumor suppressor gene in skin carcinogenesis mediated by UVB radiation, observing that exposed knockout mice developed this type of NMSC. […] Recently, studies with whole-exome sequencing (WES) described the prevalence of oncogenic variants on this gene in 60% of the analyzed samples, in contrast to the adjacent UV-exposed epidermis. […] The immune system and its regulation are essential in NMSC emergence and tumor microenvironment establishment. […] Indeed, UVB radiation also has an impact on the immune response, which can induce immunosuppression, such as a reduction in Langerhans cell (from the skin immune system) antigen-presenting capacity, due to apoptosis and lymph node migration. […] The combination of UVB-induced ROS, DNA damage, cytokines, and chemokines release affects epidermal cells’ stability.

• #41 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  In the pathogenesis of NMSC and AKs different factors play an important role, including UV rays, X-rays, HPV, arsenic compounds, and other chemical products. […] As reported by several papers, the primary risk factor for cutaneous carcinogenesis is cumulative UV exposure from sunlight and/or tanning beds, which lead to UV-induced alteration in skin protein expression. […] UV exposure is considered as a complete carcinogen, since it affects each stage of carcinogenesis. In fact, it leads to cellular damage because of the reduction of cell-mediated immune responses, production of reactive oxygen species (ROS) and DNA alteration. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. […] It has been suggested that exposure to chronic UVB radiation determines heparanase activation, which causes the degradation of heparin sulfate and increments the interaction between the epidermal growth factor and the dermis.

• #42 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  Therefore, heparanase is involved in BCC and SCC formation. […] In addition, UV exposure affects the p53 expression, which is altered in both AKs and SCC. […] X-rays play a role in the pathogenesis of NMSC. […] It has been reported that several class I and class II HLA allele groups were associated with SCC in immunosuppressed patients, including HLA-B*27, HLA-A*03 and HLA-DQA1*01. […] Immunosuppression also plays a role in carcinogenesis, leading to an easier NMSC development. […] The risk of developing SCC is also increased by exposure to carcinogenic chemicals, above all arsenic. […] The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy. […] Non-melanoma skin cancers (NMSCs) are the most common malignancy worldwide, of which 99% are basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of skin.

• #43 Current status of skin cancers with a focus on immunology and immunotherapy | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-03012-7

  However, SCCs are driven by several mutated genes. […] Certain oncogenic viruses such as HPV, EBV, and the recently discovered Merkel Cell Polyomavirus (McPhee) have been found to possess oncogenic potential for NMSCs. […] The E6 and E7 oncoproteins produced by HPV can integrate into the host’s keratinocyte genome. […] The development of an effective skin cancer prevention strategy requires a comprehensive understanding of the risk factors involved. Non-melanoma skin cancers (NMSCs) can be categorized into two groups: individual and environmental factors. […] The most notable individual risk factors include age, gender, and genetics. Meanwhile, exposure to ultraviolet (UV) radiation is the primary environmental factor. […] The incidence of squamous cell carcinoma (SCC) increases at a faster rate with age than basal cell carcinoma (BCC).

• #44 Current status of skin cancers with a focus on immunology and immunotherapy | Cancer Cell International | Full Text

  https://cancerci.biomedcentral.com/articles/10.1186/s12935-023-03012-7

  However, SCCs are driven by several mutated genes. […] Certain oncogenic viruses such as HPV, EBV, and the recently discovered Merkel Cell Polyomavirus (McPhee) have been found to possess oncogenic potential for NMSCs. […] The E6 and E7 oncoproteins produced by HPV can integrate into the host’s keratinocyte genome. […] The development of an effective skin cancer prevention strategy requires a comprehensive understanding of the risk factors involved. Non-melanoma skin cancers (NMSCs) can be categorized into two groups: individual and environmental factors. […] The most notable individual risk factors include age, gender, and genetics. Meanwhile, exposure to ultraviolet (UV) radiation is the primary environmental factor. […] The incidence of squamous cell carcinoma (SCC) increases at a faster rate with age than basal cell carcinoma (BCC).

• #45 Serine and one-carbon metabolism sustain non-melanoma skin cancer progression | Cell Death Discovery

  https://www.nature.com/articles/s41420-023-01398-x

  Tissues analysis shows that these two enzymes are mainly expressed in the proliferative areas of cBCC and in the poorly differentiated areas of cSCC, suggesting their role in tumor proliferation maintenance. […] Moreover, in vitro silencing of SHMT2 and MTHFD2 impairs the proliferation of epidermoid cancer cell line. […] Taken together these data allow us to link the central cellular metabolism (serine and/or OCM) and NMSC proliferation and progression, offering the opportunity to modulate pharmacologically the involved enzymes activity against this type of human cancer. […] A crucial step of NMSC and HNSCC development is the alteration of normal epidermal cell proliferation; indeed, several studies report that cancer cells can adapt their metabolism to achieve this effect. […] The term one-carbon metabolism (OCM) refers to a complex metabolic pathway involved in the generation of one-carbon units (hydroxymethyl groups) used by the cells for the biosynthesis of fundamental anabolic precursors, for cellular redox homeostasis and for methylation reactions.

• #46 Serine and one-carbon metabolism sustain non-melanoma skin cancer progression | Cell Death Discovery

  https://www.nature.com/articles/s41420-023-01398-x

  In general, the alteration of serine and OCM is strongly associated with different types of cancer with a high rate of cellular proliferation. […] The OCM reactions have a pivotal role in the production of pyrimidine and purine nucleotides (DNA and RNA synthesis), S-adenosylmethionine (SAM), necessary for DNA methylation and to produce reduced GSH for ROS scavenging. […] Closely related to OCM is the serine biosynthesis pathway, an alternative route of glycolysis in which glucose is converted in serine through the action of three enzymes: phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH). […] In general, the interconnection of serine anabolic/catabolic reactions and OCM are a crucial metabolic hub for cellular energy production, regulation of proliferation rate, and cellular differentiation and for these reasons it is essential to describe a possible way to reprogram these metabolisms in cancer.

• #47 Serine and one-carbon metabolism sustain non-melanoma skin cancer progression | Cell Death Discovery

  https://www.nature.com/articles/s41420-023-01398-x

  Non-melanoma skin cancer (NMSC) is a tumor that arises from human keratinocytes, showing abnormal control of cell proliferation and aberrant stratification. […] From a molecular point of view, we are still far from fully understanding the molecular mechanisms behind the onset and progression of NMSC and to unravel targetable vulnerabilities to leverage for their treatment, which is still essentially based on surgery. […] Therefore, our work is based on the characterization of the serine anabolism/catabolism and/or one-carbon metabolism (OCM) role in NMSC pathogenesis. […] Expression and protein analysis of normal skin and NMSC samples show the alteration of the expression of two enzymes involved in the serine metabolism and OCM, the Serine Hydroxy-Methyl Transferase 2 (SHMT2) and Methylen-ThetraHydroFolate dehydrogenase/cyclohydrolase 2 (MTHFD2).

• #48 Serine and one-carbon metabolism sustain non-melanoma skin cancer progression | Cell Death Discovery

  https://www.nature.com/articles/s41420-023-01398-x

  Tissues analysis shows that these two enzymes are mainly expressed in the proliferative areas of cBCC and in the poorly differentiated areas of cSCC, suggesting their role in tumor proliferation maintenance. […] Moreover, in vitro silencing of SHMT2 and MTHFD2 impairs the proliferation of epidermoid cancer cell line. […] Taken together these data allow us to link the central cellular metabolism (serine and/or OCM) and NMSC proliferation and progression, offering the opportunity to modulate pharmacologically the involved enzymes activity against this type of human cancer. […] A crucial step of NMSC and HNSCC development is the alteration of normal epidermal cell proliferation; indeed, several studies report that cancer cells can adapt their metabolism to achieve this effect. […] The term one-carbon metabolism (OCM) refers to a complex metabolic pathway involved in the generation of one-carbon units (hydroxymethyl groups) used by the cells for the biosynthesis of fundamental anabolic precursors, for cellular redox homeostasis and for methylation reactions.

• #49 Adhesion Molecules in Non-melanoma Skin Cancers: A Comprehensive Review | In Vivo

  https://iv.iiarjournals.org/content/35/3/1327

  Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently diagnosed cancers, generating significant medical and financial problems. Cutaneous carcinogenesis is a very complex process characterized by genetic and molecular alterations, and mediated by various proteins and pathways. Cell adhesion molecules (CAMs) are transmembrane proteins responsible for cell-to-cell and cell-to-extracellular matrix adhesion, engaged in all steps of tumor progression. […] The differences in expression of adhesion molecules may be related to the invasiveness of these tumors, through the loss of tissue integrity, neovascularization and alterations in intercellular signaling processes. […] Changes in the expression or function of cell adhesion molecules (CAM) are involved in all steps of the progression of the malignancy, starting from the detachment of tumor cells from the primary site, intravasation into the blood, extravasation into distant tissues and formation of the secondary lesions. […] Numerous studies indicate that differences in the expression of adhesion molecules are related to the invasiveness of skin cancers. Downregulation of some, physiologically present, adhesion molecules has been recently suggested to be a sign of a higher tumor metastatic potential.

• #50 Adhesion Molecules in Non-melanoma Skin Cancers: A Comprehensive Review | In Vivo

  https://iv.iiarjournals.org/content/35/3/1327

  Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently diagnosed cancers, generating significant medical and financial problems. Cutaneous carcinogenesis is a very complex process characterized by genetic and molecular alterations, and mediated by various proteins and pathways. Cell adhesion molecules (CAMs) are transmembrane proteins responsible for cell-to-cell and cell-to-extracellular matrix adhesion, engaged in all steps of tumor progression. […] The differences in expression of adhesion molecules may be related to the invasiveness of these tumors, through the loss of tissue integrity, neovascularization and alterations in intercellular signaling processes. […] Changes in the expression or function of cell adhesion molecules (CAM) are involved in all steps of the progression of the malignancy, starting from the detachment of tumor cells from the primary site, intravasation into the blood, extravasation into distant tissues and formation of the secondary lesions. […] Numerous studies indicate that differences in the expression of adhesion molecules are related to the invasiveness of skin cancers. Downregulation of some, physiologically present, adhesion molecules has been recently suggested to be a sign of a higher tumor metastatic potential.

• #51 Adhesion Molecules in Non-melanoma Skin Cancers: A Comprehensive Review | In Vivo

  https://iv.iiarjournals.org/content/35/3/1327

  Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently diagnosed cancers, generating significant medical and financial problems. Cutaneous carcinogenesis is a very complex process characterized by genetic and molecular alterations, and mediated by various proteins and pathways. Cell adhesion molecules (CAMs) are transmembrane proteins responsible for cell-to-cell and cell-to-extracellular matrix adhesion, engaged in all steps of tumor progression. […] The differences in expression of adhesion molecules may be related to the invasiveness of these tumors, through the loss of tissue integrity, neovascularization and alterations in intercellular signaling processes. […] Changes in the expression or function of cell adhesion molecules (CAM) are involved in all steps of the progression of the malignancy, starting from the detachment of tumor cells from the primary site, intravasation into the blood, extravasation into distant tissues and formation of the secondary lesions. […] Numerous studies indicate that differences in the expression of adhesion molecules are related to the invasiveness of skin cancers. Downregulation of some, physiologically present, adhesion molecules has been recently suggested to be a sign of a higher tumor metastatic potential.

• #52 Adhesion Molecules in Non-melanoma Skin Cancers: A Comprehensive Review | In Vivo

  https://iv.iiarjournals.org/content/35/3/1327

  Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently diagnosed cancers, generating significant medical and financial problems. Cutaneous carcinogenesis is a very complex process characterized by genetic and molecular alterations, and mediated by various proteins and pathways. Cell adhesion molecules (CAMs) are transmembrane proteins responsible for cell-to-cell and cell-to-extracellular matrix adhesion, engaged in all steps of tumor progression. […] The differences in expression of adhesion molecules may be related to the invasiveness of these tumors, through the loss of tissue integrity, neovascularization and alterations in intercellular signaling processes. […] Changes in the expression or function of cell adhesion molecules (CAM) are involved in all steps of the progression of the malignancy, starting from the detachment of tumor cells from the primary site, intravasation into the blood, extravasation into distant tissues and formation of the secondary lesions. […] Numerous studies indicate that differences in the expression of adhesion molecules are related to the invasiveness of skin cancers. Downregulation of some, physiologically present, adhesion molecules has been recently suggested to be a sign of a higher tumor metastatic potential.

• #53 Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2017.5817

  Nonmelanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. […] It has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. […] Studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). […] The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene-related peptide and somatostatin. […] There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC.

• #54 Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2017.5817

  Nonmelanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. […] It has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. […] Studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). […] The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene-related peptide and somatostatin. […] There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC.

• #55 Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2017.5817

  Nonmelanoma skin cancer (NMSC) is the most common form of cancer worldwide, comprising 95% of all cutaneous malignancies and approximately 40% of all cancers. […] It has been shown that ultraviolet radiation is, in the majority of cases, the main trigger involved in the pathogenesis of NMSC. […] Studies have indicated that several neuroactive factors are involved in the carcinogenesis of two of the most common types of NMSC, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). […] The complex interaction between the peripheral nervous system and target cells in the skin appears to be mediated by locally released neuroendocrine factors, such as catecholamines, substance P, calcitonin gene-related peptide and somatostatin. […] There is also a significant body of evidence indicating that psychological stress is a crucial impact factor influencing the course of skin cancers, including SCC and BCC.

• #56 Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2017.5817

  Numerous studies have suggested that neuroendocrine factor dysregulation, as observed in stress reactions, may be involved in tumorigenesis, accelerating the development and progression, and suppressing the regression of NMSC. […] The fact that NMSC arises mostly on sun-exposed areas has highlighted the crucial role of UVR in the pathogenesis of NMSC. […] The immunosuppressive-inducing effects of UVR are primarily cited as conditioning a permissive tumor microenvironment for BCC and SCC. […] Various studies have suggested a link between neuroendocrine factors and skin carcinogenesis in the two most common types of NMSC, BCC and SCC. […] The mechanisms through which neuroendocrine factors influence mucocutaneous physiopathological processes are extremely complex, involving the dysregulation of the dynamic balance between the nervous, endocrine and immune systems.

• #57 Neuroendocrine factors: The missing link in non‑melanoma skin cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2017.5817

  A key function of physiological mediators released in short-term stress reactions may be to ensure that the proper cells (e.g., leukocytes) are in the right place, at the right time, and that they are activated appropriately to be able to respond to the immune challenge posed by the stressor. […] Although acute stress seems to play a rather protective role in the context of carcinogenesis for the aforementioned reasons, chronic stress, acting through the plethora of neuropeptides, neurohormones and cytokines involved, leads to chronic immunosuppression and, as a result, promotes a favorable environment for NMSC carcinogenesis.

• #58 Nonmelanoma skin cancer – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/nonmelanoma-skin-cancer/symptoms-causes/syc-20355397

  Nonmelanoma skin cancer develops when changes happen in the DNA of skin cells. […] In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. In nonmelanoma skin cancer, the cells grow out of control and may form a new growth on the skin or cause changes in an existing spot on the skin. […] Ultraviolet light, also called UV light, causes most of the DNA changes in skin cells. UV light can come from sunlight, tanning lamps and tanning beds. But sun exposure doesn’t explain skin cancers that develop on skin that’s not typically exposed to sunlight. Other factors can contribute to the risk and development of nonmelanoma skin cancer. The exact cause is not always clear.

• #59 Nonmelanoma skin cancer – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/nonmelanoma-skin-cancer/symptoms-causes/syc-20355397

  Nonmelanoma skin cancer develops when changes happen in the DNA of skin cells. […] In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. In nonmelanoma skin cancer, the cells grow out of control and may form a new growth on the skin or cause changes in an existing spot on the skin. […] Ultraviolet light, also called UV light, causes most of the DNA changes in skin cells. UV light can come from sunlight, tanning lamps and tanning beds. But sun exposure doesn’t explain skin cancers that develop on skin that’s not typically exposed to sunlight. Other factors can contribute to the risk and development of nonmelanoma skin cancer. The exact cause is not always clear.

• #60 Advances in Skin Cancer | IntechOpen

  https://www.intechopen.com/chapters/1177229

  Skin cancer has been associated with excessive sun exposure ever since the nineteenth century. […] Cumulative exposure to ultraviolet radiation mainly from the sun results in DNA damage, oxidative stress, inflammatory response, and gene mutations, all leading to the development of skin cancer. […] Many molecular pathways are affected by the mutations and can activate oncogenes, inactivate tumor suppressor genes, or impair DNA repair genes. This consequently can lead to increased proliferation, blood vessel growth, tumor invasion, evasion of immune response, and ultimately, metastasis. […] Non-melanoma skin cancers arise via a multistep process, gradually acquiring mutations and progressing to precancerous lesions such as actinic keratosis (AK), keratosis, dermatitis, scars, chronic ulcers, or Bowens disease (BD).

• #61 Advances in Skin Cancer | IntechOpen

  https://www.intechopen.com/chapters/1177229

  Recent studies have shown that UVR-induced signal transduction plays a huge role in the initiation and progression of non-melanoma cancer and is remarkably complex. […] Common mutations found in cSCC include those in RAS oncogene, which encodes RAS protein. This gene plays a crucial role in the evolution of non-melanoma carcinomas through regulation of proliferation, apoptosis, and angiogenesis. […] BCC originates from pluripotent interfollicular stem cells and involves mainly a mutation in the sonic Hedgehog signaling pathway as a result of high exposure to UV radiation in 90% of the cases. […] Another common affected pathway in BCC is found on the Canonical (-catenin dependent) Wingless (WNT) signaling pathway.

• #62 Narrative review: mechanism of ultraviolet radiation-induced basal cell carcinoma – Fan – Frontiers of Oral and Maxillofacial Medicine

  https://fomm.amegroups.org/article/view/55995/html

  Aberrant HH signaling activation is a hallmark of basal cell carcinogenesis. […] The oncogene P53 is involved in the regulation of the cell cycle and the activation of programmed cell death. […] RAS genes are divided into three proto-oncogenes, H-ras, K-ras, and N-ras, which together encode 21 kDa proteins. […] UVR-induced immunosuppression plays a crucial role in skin carcinogenesis. […] UVR significantly reduces the antigen-presenting capacity of skin dendritic cells, thereby suppressing the local immune response and promoting the evasion of tumor immune surveillance by premalignant and early melanoma cells. […] As solar UVR is the most important environmental risk factor for the development of BCC, protection against UVR is a fundamental approach to preventing BCC.

• #63 Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/es-resistance-nonmelanoma-skin-cancer-nonsurgical-articulo-S1578219016302219

  Resistance is generally thought to be due to intrinsic factors inherent to the tumor cells or extrinsic factors in the tumor environment, which has an important role in treatment response through the establishment of gradients in factors such as signaling, O2, and metabolites. […] Intrinsic resistance may be due to a complex set of factors, including aspects related to the expression of genes involved in the genesis of NMSC and other aspects related to the photodynamic process itself. […] UV light-induced DNA mutations in tumor suppressor genes, such as p53, are common and have been described as early events in the carcinogenesis of 50% of BCCs and AKs and in 90% of SCCs. […] The oxidative stress caused by PDT activates signaling cascades involved in survival, proliferation, and inhibition of apoptosis mediated by protein kinase B (PKB/Akt), nuclear factor k (NF-kB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and cyclooxygenase-2 (COX-2), as well as genes involved in the antioxidant response pathway, such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) gene.

• #64 Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/es-resistance-nonmelanoma-skin-cancer-nonsurgical-articulo-S1578219016302219

  Resistance is generally thought to be due to intrinsic factors inherent to the tumor cells or extrinsic factors in the tumor environment, which has an important role in treatment response through the establishment of gradients in factors such as signaling, O2, and metabolites. […] Intrinsic resistance may be due to a complex set of factors, including aspects related to the expression of genes involved in the genesis of NMSC and other aspects related to the photodynamic process itself. […] UV light-induced DNA mutations in tumor suppressor genes, such as p53, are common and have been described as early events in the carcinogenesis of 50% of BCCs and AKs and in 90% of SCCs. […] The oxidative stress caused by PDT activates signaling cascades involved in survival, proliferation, and inhibition of apoptosis mediated by protein kinase B (PKB/Akt), nuclear factor k (NF-kB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and cyclooxygenase-2 (COX-2), as well as genes involved in the antioxidant response pathway, such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) gene.

• #65 Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/es-resistance-nonmelanoma-skin-cancer-nonsurgical-articulo-S1578219016302219

  Resistance is generally thought to be due to intrinsic factors inherent to the tumor cells or extrinsic factors in the tumor environment, which has an important role in treatment response through the establishment of gradients in factors such as signaling, O2, and metabolites. […] Intrinsic resistance may be due to a complex set of factors, including aspects related to the expression of genes involved in the genesis of NMSC and other aspects related to the photodynamic process itself. […] UV light-induced DNA mutations in tumor suppressor genes, such as p53, are common and have been described as early events in the carcinogenesis of 50% of BCCs and AKs and in 90% of SCCs. […] The oxidative stress caused by PDT activates signaling cascades involved in survival, proliferation, and inhibition of apoptosis mediated by protein kinase B (PKB/Akt), nuclear factor k (NF-kB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and cyclooxygenase-2 (COX-2), as well as genes involved in the antioxidant response pathway, such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) gene.

• #66 Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/es-resistance-nonmelanoma-skin-cancer-nonsurgical-articulo-S1578219016302219

  Resistance to treatment, however, has also been reported since the approval of vismodegib. […] Current research efforts are focused on new therapeutic targets and the development of second-generation inhibitors that remain active in the presence of mutations. […] Despite an initial favorable response, patients treated with SMO inhibitors develop resistance due to compensatory mechanisms generated over time. […] A wide variety of mechanisms have been described for resistance of NMSC to nonsurgical treatments. They include mechanisms related to intracellular drug transport (e.g., Ppg in PDT), mutations in target genes such as SMO with vismodegib, alterations to molecular pathways such as MAPK in PDT and EGFR inhibitors and even intrinsic cell characteristics such as adhesion molecules, cytoskeleton components, size, and tumor progression.

• #67 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  The biology of cancer is complex, and NMSC is the most frequent type of skin cancer worldwide. […] Environmental risk factors such as UVB radiation from sunlight can directly damage the DNA of epidermal cells. […] Genetic features and failure in DNA repair mechanisms continue to be a determinant of cancer susceptibility. […] However, these features may represent an opportunity to advance in new therapies’ development that not only focus on removing cancer cells, as the source of tumor origin, but also on a sequence of immunological, genetic, epigenetic, and stromal events. […] Recognizing tumors as pieces of a machine for growth factors, inflammatory molecules, and extracellular matrix protein production, functioning together for cancer establishment and progression, may be crucial for successful cancer treatment.

• #68 Non Melanoma Skin Cancer Pathogenesis Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5874663/

  (1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; […] (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; […] (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development.

• #69 Non-Melanoma Skin Cancer: A Genetic Update and Future Perspectives

  https://www.mdpi.com/2072-6694/14/10/2371

  The biology of cancer is complex, and NMSC is the most frequent type of skin cancer worldwide. […] Environmental risk factors such as UVB radiation from sunlight can directly damage the DNA of epidermal cells. […] Genetic features and failure in DNA repair mechanisms continue to be a determinant of cancer susceptibility. […] However, these features may represent an opportunity to advance in new therapies’ development that not only focus on removing cancer cells, as the source of tumor origin, but also on a sequence of immunological, genetic, epigenetic, and stromal events. […] Recognizing tumors as pieces of a machine for growth factors, inflammatory molecules, and extracellular matrix protein production, functioning together for cancer establishment and progression, may be crucial for successful cancer treatment.

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