Materiały źródłowe

• #1 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.

• #2 Non Melanoma Skin Cancer Pathogenesis Overview

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

  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; […] 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; […] 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.

• #3 Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-023-01854-3

  Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. […] To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. […] The etiology primarily lies beside the abnormal skin cell proliferation facilitated by the unrepaired DNA of skin cells which owes to DNA mutations or genetic defects. […] Cancer cells that emerge from mutations in skin melanocytes are termed malignant melanoma. […] Non-melanoma skin cancer (NMSC), which develops from the epidermis, is the kind of skin cancer that is most often seen worldwide. […] The most common reason for NMSC occurrence is Ultraviolet (UV) rays have a high risk in persons with lighter shade.

• #4 Pathophysiology of skin cancer | PPT

  https://www.slideshare.net/slideshow/pathophysiology-of-skin-cancer/15134892

  Cancer starts when cells in a part of the body grow out of control and do not die like normal cells. Instead, cancer cells continue to multiply and form abnormal cells that can invade other tissues. The pathophysiological mechanism of skin cancer involves sunlight exposure causing DNA damage through the formation of thymine dimers, which overwhelms the DNA repair process and results in mutations if the cumulative damage is not removed. This leads to decreased immune surveillance and local immune suppression, allowing abnormal cells to proliferate into tumors. […] Skin cancer is the most common form of cancer in the United States and arises from DNA mutations in skin cells. The three main types are basal cell carcinoma, squamous cell carcinoma, and melanoma. Basal and squamous cell carcinomas are common, locally destructive cancers but rarely spread, while melanoma is less common but more dangerous as it can spread.

• #5 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Skin-Cancer-Pathology.aspx

  Cancer begins when cells in a part of the body grow without control. […] Most basal cell and squamous cell skin cancers are caused by skin exposure to ultraviolet rays from sunlight and from artificial sources of such rays like tanning beds and sunlamps. […] Several genes have been noted to have associations with skin cancers. […] Cancers are caused when DNA changes turn on oncogenes or turn off tumor suppressor genes. […] Common genes that underlie squamous cell cancers include TP53. This is a tumor suppressor gene that causes cells with damaged DNA to die. […] A gene commonly affected in basal cell cancers includes the patched (PTCH) gene, which is part of the hedgehog signalling pathway. […] Apart from UV radiations from sunlight, viruses like Human Papilloma virus (HPV) also can causes changes in DNA leading to skin cancers.

• #6 Non Melanoma Skin Cancer Pathogenesis Overview

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

  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. […] 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. […] Both basal cells and squamous cells belong to keratinocytes, therefore sometimes BCC and SCC are termed keratinocyte cancer. […] One shared characteristic of skin cancer is that, according to the current views, they all are caused by solar or artificial ultraviolet radiation (UVR). […] Although skin carcinogenesis is still not fully understood, several papers have demonstrated the presence of genetic and molecular alterations involved in this process.

• #7 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.

• #8 Non Melanoma Skin Cancer Pathogenesis Overview

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

  BCC is characterized by cells that resemble epidermal basal cells and it is the least aggressive NMSC. […] However, ultraviolet (UV) radiation plays the most important role in BCC pathogenesis, although the relationship between UV radiation and BCC development remains highly controversial. […] SCC is characterized by atypical proliferation of invasive squamous cells, which could metastatize. […] However, the most important risk factor is represented by UV radiation and sunlight. […] 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.

• #9 Non Melanoma Skin Cancer Pathogenesis Overview

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

  BCC is characterized by cells that resemble epidermal basal cells and it is the least aggressive NMSC. Indeed, BCC shows a low degree of malignancy, despite of the capability of local invasion, tissue destruction, recurrence, and a limited potential for metastasis. […] However, ultraviolet (UV) radiation plays the most important role in BCC pathogenesis, although the relationship between UV radiation and BCC development remains highly controversial. […] Chronic exposure to nonionizing solar radiation, specifically UVA and UVB, is the most important risk factor in BCC pathogenesis. […] 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 Genetics of Skin Cancer (PDQ®) – NCI

  https://www.cancer.gov/types/skin/hp/skin-genetics-pdq

  An autosomal recessive disease, called xeroderma pigmentosum (XP), is associated with increased BCC, SCC, and melanoma risks. […] The true cytologic origin of BCC is unclear. BCC and basal cell keratinocytes share many histological similarities, as is reflected in the name. Alternatively, the outer root sheath cells of the hair follicle have also been proposed as the cell of origin for BCC. […] Some debate remains about the origin of SCC; however, these cancers are likely derived from epidermal stem cells associated with the hair follicle. […] Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can undergo malignant transformation into melanoma. Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age.

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

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

  Basal cell carcinoma (BCC) is a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells (ie, small, round cells found in the lower layer of the epidermis). […] Most of the DNA alterations involved in BCC result from damage caused by exposure to sunlight, but inheritance may be a factor in some cases. […] The patched/hedgehog intracellular signaling pathway plays a role in both sporadic BCCs and nevoid BCC syndrome (Gorlin syndrome). This pathway influences differentiation of various tissues during fetal development. After embryogenesis, it continues to function in regulation of cell growth and differentiation. Loss of inhibition of this pathway is associated with human malignancy, including BCC. […] When SHH is present, it binds to PTCH, which then releases and activates SMO. SMO signaling is transduced to the nucleus via Gli. When SHH is absent, PTCH binds to and inhibits SMO. Mutated forms of PTCH are unable to bind to SMO, simulating the presence of SHH. The unbound SMO and downstream Gli are constitutively activated, thereby allowing hedgehog signaling to proceed unimpeded. The same pathway may also be activated via mutations in the SMO gene, which also allows unregulated signaling of tumor growth.

• #12 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. […] 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. […] Indeed, cutaneous SCC is thought to arise via a multistep process, gradually acquiring mutations that lead to more aggressive behavior. […] 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. […] It has been postulated that 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.

• #13 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.

• #14 Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-023-01854-3

  The mainstay of treating CSCC is surgery, though radiation is occasionally used as well. […] However, some individuals with locally progressed and metastatic CSCC might gain from systemic therapies. […] The prognosis for individuals with cutaneous melanoma depends on the depth and location of the initial tumor, as well as whether or not they have localized or distant metastatic disease. […] Melanoma are aggressive malignant tumors that arise from melanocytes. […] A buildup of genetic alterations that activate oncogenes, deactivate tumor suppressor genes and hinder DNA repair when organisms are exposed to ultraviolet radiation. […] This mechanism may result in unchecked melanocyte growth and ultimately malignancy. […] The prognosis for individuals with cutaneous melanoma depends on the depth and location of the initial tumor, as well as whether or not they have localized or distant metastatic disease.

• #15 Signal pathways of melanoma and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-021-00827-6

  Melanoma is the most lethal skin cancer that originates from the malignant transformation of melanocytes. […] Therefore, it is necessary to understand the mechanisms underlying melanoma pathogenesis more comprehensively, which might lead to more substantial progress in therapeutic approaches and expand clinical options for melanoma therapy. […] The signal pathways orchestrating melanoma pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, and pro-angiogenic factors, have been systemically reviewed and discussed. […] The risk factors of melanoma supported by strong epidemiologic evidence include UVR, multiple moles, family history (a family history/personal history of melanoma), and fair skin, eye, and hair.

• #16 Melanoma Mechanism and Characteristics – Skin Cancer – Dermatology – Picmonic for Medicine

  https://www.picmonic.com/pathways/medicine/courses/standard/dermatology-10689/skin-cancer-39080/melanoma-mechanism-and-characteristics_1421

  Melanoma, in roughly 40% of patients, is driven by activating a mutation in B-RAF kinase. […] UV radiation from sunlight exposure and tanning beds is a carcinogen. The p16 pathway is favored at low doses of UV radiation and results in cell-cycle arrest. On the contrary, the p53 pathway is more responsive to higher doses and induces apoptosis depending on p53 mutation status. […] About 40% of human melanomas contain activating mutations affecting the structure of the B-Raf kinase protein. […] The risk of melanoma is more than 10 times higher for whites than for African Americans. […] The early stage of the disease is known as the radial growth phase when the tumor is less than 1 mm thick. […] As the cancer cells have not yet reached the blood vessels lower in the skin, it is very unlikely that this early-stage cancer will metastasize to other parts of the body. […] The following step in the process is the invasive melanoma, the vertical growth phase. […] During the vertical growth phase, the depth of tumor invasion correlates with the risk of metastasis.

• #17 Skin Cancer Information

  https://www.skincancer.org/skin-cancer-information/

  Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The main types of skin cancer are basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma and Merkel cell carcinoma (MCC). […] The two main causes of skin cancer are the sun’s harmful ultraviolet (UV) rays and using UV tanning beds. […] Most BCCs are caused by the combination of intermittent, intense exposure and cumulative, long-term exposure to UV radiation from the sun. […] Cumulative, long-term exposure to UV radiation from the sun and tanning beds causes most SCCs. […] Melanoma is often triggered by the kind of intense, intermittent sun exposure that leads to sunburn. Tanning bed use also increases risk for melanoma. […] Usually associated with a virus called the Merkel cell polyomavirus, MCCs most often arise on sun-exposed areas in fair-skinned individuals over age 50.

• #18 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.

• #19 Molecular Mechanisms and Biomarkers of Skin Photocarcinogenesis | IntechOpen

  https://www.intechopen.com/chapters/57023

  Skin cancer is the most commonly diagnosed malignancy in the United States and worldwide. […] Improved understanding of the molecular pathways underlying skin cancer pathogenesis has led to the investigation of new approaches to skin cancer prevention. […] While numerous attempts have been made to reduce skin cancer risk factors related to ultraviolet radiation exposure, skin cancer incidence continues to rise. […] UVR exposure and age are the leading risk factors in skin cancer pathogenesis. […] It is estimated that approximately 90% of NMSCs are associated with excessive exposure to UVR and incidence increases with age. […] The link between UVR exposure and NMSC is well established. […] UVR is recognized to induce a specific pattern of genetic mutations, namely CT and CCTT substitutions.

• #20

  https://link.springer.com/article/10.1007/s42764-020-00009-8

  Ultraviolet (UV) irradiation causes various types of DNA damage, which leads to specific mutations and the emergence of skin cancer in humans, often decades after initial exposure. […] A major role in inducing sunlight-dependent skin cancer mutations is assigned to the cyclobutane pyrimidine dimers (CPDs). […] Epidemiological evidence clearly points to solar ultraviolet radiation as an overwhelming cause of skin cancer. […] The damage to DNA caused by UV radiation can be direct or indirect. The direct DNA damage consists predominantly of dimerized pyrimidines, and it is this type of damage that is likely the most relevant for skin cancer induction. […] CPDs are the major DNA damage product in simulated sunlight (UVA+UVB)-irradiated DNA or cells. […] Taken together, the accumulated data suggest that CPDs are the major mutagenic DNA lesions produced by terrestrial sunlight in the skin.

• #21 Skin cancer – Wikipedia

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

  UV-irradiation of skin cells causes damage to DNA through photochemical reactions. Cyclobutane pyrimidine dimers formed by adjacent thymine bases, or by adjacent cytosine bases, are frequent types of DNA damage induced by UV. Human skin cells are capable of repairing most UV-induced damage by nucleotide excision repair, a process that protects against skin cancer, but may be inadequate at high levels of exposure. […] A molecular factor involved in the disease process is mutation in gene PTCH1 that plays an important role in the Sonic hedgehog signaling pathway.

• #22 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

  This review highlights UVR damages DNA and its repair mechanisms, suppression the immune system, causes progressive gene mutations, and ultimately leads to tumor formation. […] UV-induced skin carcinogenesis is a complex and sequential biological process caused by different wavelengths of UV light. […] UVB can be absorbed directly by DNA, leading to DNA damage and altered gene expression through intracellular signal transduction, which can induce skin cancer. […] Cells could repair damaged DNA, but DNA repair may go wrong due to genetic or environmental factors. […] Therefore, the mutation of proto-oncogenes and suppressor genes may occur, leading to the formation of tumors. […] UVR causes damage to DNA and its repair system and changes the immune system, leading to progressive genetic changes and tumor formation.

• #23 Etiology and pathogenesis of basal cell carcinoma

  https://sciendo.com/article/10.2478/sjdv-2013-0009

  Basal cell carcinoma (BCC) is the most common cancer among Caucasians. It generally occurs on sun-exposed areas of the body, mostly on the head and neck (80%), trunk (15%), rarely on arms and legs. Basal cell carcinoma is a good example of a disease caused by a combination of genetic and environmental factors. Ultraviolet (UV) radiation plays a dual role in the development of BCC: it causes DNA damage and immunosuppression. UVA and UVB rays damage the DNA via various mechanisms. UVB radiation directly damages DNA within skin cells, causing cytosine thymine mutations at dipyrimidine sites, whereas UVA radiation is 10.000 times less mutagenic, but it is significantly more present in the natural UV radiation. […] UV radiation exerts immune suppression by decreasing the antigen presenting cells ability and by producing immunosuppressive cytokines, such as interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-).

• #24 Signal pathways of melanoma and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-021-00827-6

  Intense UVR can induce genetic alterations like DNA damage and genetic mutation, reactive oxygen species (ROS) accumulation, and oxidative stress, as well as inflammatory responses involving macrophages and neutrophils infiltration, which are related to malignant switch of melanocytes. […] The therapeutic approaches of melanoma undergo a dramatic evolution in the past few decades due to the progress in the understanding of melanoma pathogenesis and thereby revolutionary advances of targeted therapies that specifically intervene mutant driver genes and immune checkpoints. […] Therefore, it is necessary to understand the molecular mechanisms underlying melanoma pathogenesis more comprehensively, which might lead to the innovations of more applicable therapeutic approaches and provide additional clinical options for melanoma therapy.

• #25 Pathophysiology of skin cancers – %%parent_title%% – PlastSurgeon

  https://plastsurgeon.com/non-melanoma-skin-cancer/pathophysiology-of-skin-cancers/

  UV light damages the DNA of the skin by inducing free radicals in the cells. Free radicals cause damage to the DNA double helix, changing the cells repairing mechanism, replication and also inhibit apoptosis (programmed cell death). The cell thereby evolves to an invasive skin cancer.

• #26 Anatomy of the Skin and the Pathogenesis of Nonmelanoma Skin Cancer | Plastic Surgery Key

  https://plasticsurgerykey.com/anatomy-of-the-skin-and-the-pathogenesis-of-nonmelanoma-skin-cancer/

  Skin is composed of the epidermis, dermis, and adnexal structures. […] The 2 most common kinds of nonmelanoma skin cancers are basal cell and squamous cell carcinoma. Both are caused by a host of environmental and genetic factors, although UV light exposure is the single greatest predisposing factor. […] Basal cell and squamous cell carcinomas are caused by a host of environmental and genetic factors. […] Langerhans cell numbers decrease with UV radiation exposure, and the consequent decrease in skin immunologic activity may create a more permissive environment for carcinoma development.

• #27 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

  UVB induces MAPK signaling pathway. […] When a foreign antigen enters the human body, the immune system becomes activated and fights against that antigen but in case of UV light, this pathway does not occur because UV could suppress the immune system and it causes insufficient prevention against tumor development as well. […] A subgroup of T regulatory cells is also induced to grow, specifically for the antigen encountered after UVR. […] Skin cancer can also result from a mutation in the P53 gene. […] Basal cell carcinoma (BCC) pathogenesis is caused by several tumor suppressor genes and proto-oncogenes, including members of the RAS family, Sonic Hedgehog pathway (PTCH1 and SMO), and the TP53 tumor suppressor gene. […] 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.

• #28 Etiology and pathogenesis of basal cell carcinoma

  https://sciendo.com/article/10.2478/sjdv-2013-0009

  Activation of Ras gene may play an important role during early stages in the development of nonmelanoma skin cancers, and it is often found on UV-exposed skin in BCC, actinic keratosis and SCC. […] Concerning immunologic factors, studies have shown that tumor necrosis factor- (TNF-) is the critical mast cell product involved in ultraviolet-induced immunosuppression: mast cells contain high quantities of TNF- which is released after activation; the level of TNF- is increased in the skin exposed to UV radiation disrupting the morphology and function of Langerhans cells, the principal antigen-presenting cells of the skin. […] It has been established that mast cell-derived histamine stimulates prostaglandin E2 (PGE2) production from keratinocytes. PGE2 alters the cytokine balance in favor of the immunosuppressive interleukin-10 (IL-10) against the immunostimulatory IL-12; histamine also increases suppressor T-cell function by binding to the H2 receptors, which in turn release higher levels of immune suppressive cytokines including IL-10 and induce apoptosis of antigen-presenting cells. All this results in a shift of the immune response from T helper 1 (Th1) cytokine profile to T helper 2 (Th2) cytokine profile, inhibiting antigen-presenting cells to induce antitumor activity.

• #29 Non Melanoma Skin Cancer Pathogenesis Overview

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

  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.

• #30 Genetics of Skin Cancer (PDQ®) – NCI

  https://www.cancer.gov/types/skin/hp/skin-genetics-pdq

  More than 100 types of tumors are clinically apparent on the skin. Many are known to have familial and/or inherited components, either in isolation or as part of a syndrome with other features. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are two of the most common malignancies in the United States and are often caused by sun exposure, although several hereditary syndromes and genes are also associated with an increased risk of developing these cancers. Melanoma (which is sometimes referred to as cutaneous melanoma) is a less common type of skin cancer, but 5% to 10% of all melanomas arise in multiple-case families and can be inherited in an autosomal dominant fashion. Melanoma is the most lethal of the common skin cancers. […] Several genes and hereditary syndromes are associated with the development of skin cancer: Basal cell nevus syndrome (BCNS, caused by pathogenic variants in PTCH1 and PTCH2) is associated with increased BCC risk. Syndromes such as oculocutaneous albinism, epidermolysis bullosa, and Fanconi anemia are associated with increased SCC risk. CDKN2A is a major germline tumor suppressor gene that is associated with increased melanoma risk. Pathogenic variants in CDKN2A may account for 35% to 40% of all familial melanomas. Germline pathogenic variants in several other genes (i.e., CDK4, MITF, and BAP1) are also associated with increased melanoma risk.

• #31 The Mechanics of Melanoma – HealthWell FoundationSearch Icon

  https://www.healthwellfoundation.org/realworldhealthcare/the-mechanics-of-melanoma/

  Melanoma is the uncontrolled growth of the pigment-producing cells known as melanocytes, which are located in the bottom layer of the skin’s top layer (the epidermis). Like other types of cancers, melanoma arises from gene mutations in these cells that impact cell growth and division. In the case of melanoma and other skin cancers, the DNA damage is usually caused by ultraviolet (UV) radiation, resulting in a tumor that initially grows in the skin, spreading along the epidermis. […] Although most cases of all types of skin cancer are traceable to excessive sun exposure, about 10% are likely due to genetic factors. The gene most commonly mutated in familial melanoma is p53. p53 is a “tumor suppressor,” which means that it detects DNA damage in cells, and triggers either DNA repair pathways or activates cell death if the DNA damage cannot be repaired.

• #32 p53 and the pathogenesis of skin cancer (Journal Article) | OSTI.GOV

  https://www.osti.gov/biblio/21077833

  The p53 tumor suppressor gene and gene product are among the most diverse and complex molecules involved in cellular functions. Genetic alterations within the p53 gene have been shown to have a direct correlation with cancer development and have been shown to occur in nearly 50% of all cancers. p53 mutations are particularly common in skin cancers and UV irradiation has been shown to be a primary cause of specific 'signature’ mutations that can result in oncogenic transformation. […] This review discusses the role of p53 from normal function and its dysfunction in pre-cancerous lesions and non-melanoma skin cancers. Additionally, special situations are explored, such as Li-Fraumeni syndrome in which there is an inherited p53 mutation, and the consequences of immune suppression on p53 mutations and the resulting increase in non-melanoma skin cancer in these patients.

• #33 Modern understanding of the pathogenesis of basal cell skin cancer – Saytburkhanov – Vestnik dermatologii i venerologii

  https://journal-vniispk.ru/0042-4609/article/view/117568

  The incidence of basal cell skin cancer is increasing worldwide. The initiation and progression of basal cell skin cancer is due to the interaction of environmental factors and the patient’s genetic characteristics. Aberrant activation of the transmission of the Hedgehog signaling pathway is the main pathogenetic pathway of carcinogenesis. […] Since basal cell skin cancer is manifested by significant variability of morphological structure, aggressiveness and response to treatment, the disclosure of the molecular genetics of pathogenesis will become the basis for developing new approaches and increasing the effectiveness of treatment, as well as overcoming tumor resistance to treatment.

• #34

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/10000/a_recent_update_on_the_connection_between_dietary.33.aspx

  The molecular mechanisms underlying BCC development involve mutations in the sonic hedgehog (SHH) signaling pathway. […] The most common mutation in BCC is in the Patched-1 (PTCH1) gene, which normally acts as a tumor suppressor by inhibiting the SHH pathway. […] The molecular mechanisms underlying SCC development involve mutations in several genes, including TP53, Cyclin-dependent kinase inhibitor 2A (CDKN2A), and Harvey rat sarcoma viral oncogene homolog (HRAS). […] The molecular mechanisms underlying melanoma development also involve mutations in several genes and pathways that regulate cell growth, division, and apoptosis. […] The BRAF and NRAS genes are members of the RAS family of genes, which regulate cell growth and division. […] Mutations in BRAF and NRAS are commonly found in melanoma and can lead to the uncontrolled growth of melanocytes and the development of tumors.

• #35 Disease Management: Nonmelanoma Skin Cancer

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

  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. Patched 1 (PTCH1), a tumor suppressor gene that negatively regulates the hedgehog signaling pathway, is the most common mutation identified in BCC. Through a series of complex interactions, the hedgehog signaling cascade has a central role in activation and repression of an important transcription factor, glioma-associated oncogene. Dysregulation of this pathway results in the development and progression of numerous malignancies, including BCC.13 Other mutations less frequently associated with BCC involve ras oncogenes and smoothened (SMO).14 […] Cumulative UV exposure is the primary etiological factor for SCC in fair-skinned individuals.55 Although UVB is mainly responsible, UVA also plays a role. 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 Many other factors associated with the pathogenesis of SCC are detailed in Table 2.

• #36 What Causes Melanoma? | Causes of Melanoma Skin Cancer | American Cancer Society

  https://www.cancer.org/cancer/types/melanoma-skin-cancer/causes-risks-prevention/what-causes.html

  The most common change in melanoma cells is a mutation in the BRAF oncogene, which is found in about half of all melanomas. […] Familial (inherited) melanomas most often have changes in tumor suppressor genes, such as CDKN2A (also known as p16), CDK4, or BAP1, that prevent these genes from doing their normal job of controlling cell growth. […] Changes in one of these genes can lead to skin cells that have trouble repairing DNA damaged by UV rays, so these people are more likely to develop melanoma, especially on sun-exposed parts of the body. […] Some of the gene changes found in melanoma cells have proven to be good targets for drugs to help treat this disease.

• #37 Signal pathways of melanoma and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-021-00827-6

  The activation of the AKT pathway is initiated by activated phosphoinositide 3-kinase (PI3K) after the stimulation by exogenous growth factors, followed by increased generation of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) that can promote the translocation of AKT to the plasma membrane for its subsequent phosphorylation and activation. […] The therapeutic approaches of melanoma undergo a dramatic evolution in the past few decades due to the progress in the understanding of melanoma pathogenesis and thereby revolutionary advances of targeted therapies that specifically intervene mutant driver genes and immune checkpoints. […] The presence of BRAF mutations has great potential in predicting an unfavorable prognosis in melanoma patients. […] The loss of NF1 or inactivating NF1 mutation are present in 46% of melanomas expressing wild-type BRAF and RAS, which leads to constitute activation of Ras by lessening its intrinsic GTPase activity and induces hyper-activation of MAPK pathway.

• #38 Etiology and pathogenesis of basal cell carcinoma

  https://sciendo.com/article/10.2478/sjdv-2013-0009

  Several studies showed a significant association between the development of BCC and sun-exposure during childhood and adolescence, and a strong relation with family history of skin cancer. […] Regarding genetic predisposition, there is glutathione S-transferase (GST) as an important part of cellular defense against endogenous and exogenous chemicals. […] PTCH is a tumor suppressor gene first identified in patients with Gorlin syndrome. Abnormal activation of this gene and its pathways result in various types of tumorigenesis. BCC is associated with homozygous PTCH gene deletion. […] With regard to acquired genetic mutations, it was found that aggressive BCCs are significantly associated with increased p53 protein expression, probably representing the mutated form, although that assertion could not be established with certainty.

• #39 Advances in Pathogenesis and Treatment of Skin Cancer

  https://www.mdpi.com/1422-0067/26/3/1255

  An important target for epigenetic therapy in melanoma is EZH2, which is involved in disease progression by negatively regulating a number of tumor suppressor genes involved in cell transformation, proliferation, senescence escape, and apoptosis. […] The review by Nicoletti and co-workers highlights the existing research supporting the theory of a possible link between the pathogenesis of basal cell carcinoma (BCC) and a dysembryogenic process, with a particular focus on the Hedgehog signaling pathway, which is crucial for embryonic development.

• #40 Signal pathways of melanoma and targeted therapy | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-021-00827-6

  In this review, we systemically summarized the signal pathways driving melanoma pathogenesis, including the main mutated driver genes and signals, key transcriptional factors and downstream molecular biology, epigenetic modification, metabolic reprogramming, crucial metastasis-related signals, and tumor-promoting inflammatory pathways and pro-angiogenic factors. […] Taken together, the above-mentioned high-frequency mutations depict the framework of the melanoma mutational landscape, and more importantly, provide multiple druggable targets for precisely intervening specific signaling pathways. […] The dysregulated activation of the AKT pathway occurs in around 70% of total melanomas, which is the result of AKT3 amplification and PTEN loss by epigenetic silencing or deletion as previously described.

• #41 The Mechanics of Melanoma – HealthWell FoundationSearch Icon

  https://www.healthwellfoundation.org/realworldhealthcare/the-mechanics-of-melanoma/

  BRAF codes for a protein required for the transmission of a growth signal from a cell surface receptor to the cell nucleus (growth signal transduction). Growth signaling is initiated by a growth factor binding to its receptor. […] A few different checkpoint inhibitor therapies have been approved to treat metastatic melanoma. These are drugs that enable killer T-cells – immune system cells that recognize and kill threats such as cancer cells – to become fully active against a tumor cell target. […] A new type of immunotherapy drug is in Phase 3 clinical development. The drug is a small molecule inhibitor of the enzyme IDO1. IDO1 helps regulatory T-cells to develop and become activated. […] Their work suggests that melanoma cells release tiny vesicles that contain microRNA, a type of regulatory RNA produced by all cells. These micro-RNA filled vesicles induce changes in the dermis – the layer of skin just below the epidermis where the melanoma begins. […] Increased understanding of the molecular pathways that contribute to melanoma’s development and spread will provide physicians with additional tools to fight those cases of metastatic melanoma that inevitably will continue to arise.

• #42 New mechanism involved in skin cancer initiation, growth and progression

  https://medicalxpress.com/news/2015-01-mechanism-involved-skin-cancer-growth.html

  New mechanism involved in skin cancer initiation, growth and progression […] Squamous cell carcinoma (SCC) represents the second most frequent skin cancer with more than half million new patients affected every year in the world. […] However, very little is yet known about the mechanisms that regulate CSCs functions. […] In a new study featured on the cover of Cell Stem Cell, researchers led by Pr. Cédric Blanpain, MD/PhD, professor and WELBIO investigator at the IRIBHM, Université libre de Bruxelles, Belgium, report the mechanisms regulating the different functions of Twist1 controlling skin tumour initiation, cancer stem cell function and tumor progression. […] Collaborating researchers demonstrated that while Twist1 is not expressed in the normal skin, Twist1 deletion prevents skin cancer formation, demonstrating the essential role of Twist1 during tumorigenesis.

• #43 The role of immune metabolism in skin cancers: implications for pathogenesis and therapy – Lu – Translational Cancer Research

  https://tcr.amegroups.org/article/view/88815/html

  The skin is a complex organ that serves as a critical barrier against external pathogens and environmental impact. Recent advances in immunometabolism have highlighted the intricate link between cellular metabolism and immune function, particularly in the context of skin cancers. […] This review aims to provide a comprehensive overview of the key metabolic pathways and adaptations that occur in immune cells during homeostasis and activation, and explore how metabolic reprogramming contributes to the pathogenesis of specific skin cancers. […] Immune cells, like all other cells in the body, require energy and biosynthetic precursors to carry out their functions. However, it has become increasingly clear that immune cells undergo dynamic metabolic reprogramming in response to activation signals, which can have profound effects on their differentiation, effector functions, and ultimately, their impact on cancer pathogenesis.

• #44 Non Melanoma Skin Cancer Pathogenesis Overview

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

  Cutaneous HPV is classified into alpha, beta and gamma types. Beta-HPV is thought to be a cofactor in SCC pathogenesis in immunosuppressed patients. […] 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. […] It has been postulated that 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. […] In addition, UV radiation also has suppressive effects on skin immunity.

• #45 Genetics of Skin Cancer (PDQ®) – NCI

  https://www.cancer.gov/types/skin/hp/skin-genetics-pdq

  The skin is significant for communication through facial expression and hand movements. […] The skin has a wide variety of functions. First, the skin is an important barrier preventing extensive water and temperature loss and providing protection against minor abrasions. […] Immunosuppression, such as when it is induced intentionally after solid-organ transplantation to reduce the risk of transplanted organ rejection, is a significant risk factor for skin cancer. […] A personal history of BCC or SCC is strongly associated with subsequent BCC or SCC. […] Inherited pathogenic variants in the gene coding for the transmembrane receptor protein PTCH1, or PTCH, are associated with basal cell nevus syndrome (BCNS), and somatic variants are associated with sporadic cutaneous BCCs. […] Pathogenic variants in the BAP1 gene are associated with an increased risk of a variety of cancers, including cutaneous melanoma and uveal melanoma.

• #46 Immune system turning on itself may trigger melanoma growth | Yale News

  https://news.yale.edu/2012/03/28/immune-system-turning-itself-may-trigger-melanoma-growth

  A new study by researchers from Yale and Johns Hopkins reveals the molecular pathway by which the bodys inflammatory immune response may trigger its own inhibition, protecting tumor cells from destruction and allowing the growth of melanoma the deadliest form of skin cancer. […] The researchers focused on a specific immune-inhibiting molecule in melanoma tumors known as B7-H1. They found that in patients whose tumors expressed B7-H1, suppression of the inflammatory immune response promoted the growth and aggressiveness of their melanoma tumors. […] Further, they uncovered the mechanism by which this happens: Tumor cells somehow utilize an active component of the immune response itself, interferon gamma, to turn on B7-H1 and protect themselves by suppressing the immune system. […] Chen said that this mechanism may be responsible for immune suppression, and therefore tumor growth, in up to 40 percent of melanoma patients. The researchers suggest that therapies that block this anti-immune pathway may benefit patients.

• #47 Researchers reveal new mechanism behind skin cancer metastasis – SciLifeLab

  https://www.scilifelab.se/news/researchers-reveal-new-mechanism-behind-skin-cancer-metastasis/

  Researchers from SciLifeLab, KTH and Stanford University, have identified a new type of cancer cells, responsible for the metastasis of skin cancer. […] These cells only make up a small part of each tumor but are highly mobile and communicate with both cancer and normal cells. […] In the study, published in the scientific journal Cell, the researchers investigated squamous cell cancer, a form of skin cancer that has a lot in common with other epithelial cell cancers in the skin, mucosa and glands. […] The researchers also discovered a specialized type of cell different from every other cell in normal tissue. These cells, called tumor-specific keratinocytes (TSK), have the ability to invade the surrounding tissue. […] In addition, they have the ability to recruit cell types that increase the tumor growth rate, facilitating their spread to other parts of the body.

• #48 Researchers discover control mechanism for melanoma skin cancer | Doherty Website

  https://www.doherty.edu.au/news-events/news/researchers-discover-control-mechanism-for-melanoma-skin-cancer

  Australian scientists have discovered how the immune system can control melanoma, a mechanism which could be used to enhance cancer treatments. […] TRM cells were able to control the tumour in the mice for the life of the animal, which is likely to equate to decades of protection in humans. […] Previous research has shown that small numbers of cancer cells persist in the body after treatment and that the immune system probably keeps the cancer cells under control but this study in mice could study the immune system directly. […] I was able to see through moving images that these TRM cells are important for maintaining the control of the tumour cells; if you remove the TRM cells you have a break in that control and the cancer can start to grow back again, Ms Park said. […] If you could make more of these TRM cells through immunotherapies, or enhance the activity of those that are already there in some way, you could boost anti-tumour immunity.

• #49 Researchers discover control mechanism for melanoma skin cancer | Doherty Website

  https://www.doherty.edu.au/news-events/news/researchers-discover-control-mechanism-for-melanoma-skin-cancer

  Senior author on the paper, University of Melbourne Associate Professor Thomas Gebhardt, Laboratory Head at the Doherty Institute, said an increase of TRM cells has already been associated with better outcomes in cancer patients, but the way they work to suppress tumours has remained unknown. […] We now have a much better understanding of which T-cells are important in controlling skin cancers and how those cells are working but there is still much more work to do to make these cells work even better, Associate Professor Gebhardt said.

• #50 Researchers decipher the mechanism that enables skin cancer to metastasize to the brain – and inhibited its spread by 80%

  https://www.newswise.com/articles/researchers-decipher-the-mechanism-that-enables-skin-cancer-to-metastasize-to-the-brain-and-inhibited-its-spread-by-80

  Researchers from Tel Aviv University deciphered, for the first time, a mechanism that enables skin cancer to metastasize to the brain and managed to delay the spread of the disease by 60% to 80% using existing treatments. […] „In an advanced stage, 90% of melanoma (skin cancer) patients will develop brain metastases,” explains Prof. Satchi-Fainaro. […] The researchers from Tel Aviv University found that in melanoma patients with brain metastases, the cancer cells „recruit” cells called astrocytes, star-shaped cells found in the spinal cord and brain which are responsible for homeostasis, or maintaining stable conditions, in the brain. […] Moreover, the cancer cells recruit the astrocytes so that they do not inhibit the spread of the metastases. […] The communication between them is reflected in the fact that the astrocytes begin to secrete a protein that promotes inflammation called MCP-1 (also known as CCL2), and in response to this, the cancer cells begin to express its receptors CCR2 and CCR4, which we suspected to be responsible for the destructive communication with the astrocytes.

• #51 New Research Elucidates the Mechanism of Skin Cancer Metastasis to the Brain and Points to Groundbreaking Treatment | Clinical And Molecular Dx

  https://www.labroots.com/trending/clinical-and-molecular-dx/23650/research-elucidates-mechanism-skin-cancer-metastasis-brain-groundbreaking-treatment?srsltid=AfmBOoplk8qO9KKTz_GQB92_wD4QvZvlsPrHQNDs3-jyWk-SaQR4QzTq

  In advanced stages of skin cancer, patients develop brain metastases about 90% of the time. […] New research from scientists at Tel Aviv University is shedding light on why brain metastases are such a common complication in late-stage melanoma. The researchers found that in melanoma patients with brain metastases, the cancer cells recruit astrocytes, star-shaped cells found in the spinal cord and brain which are responsible for maintaining stable conditions in the brain. […] As the cancer cells recruit astrocytes, they create local inflammation in areas that increase permeability through the blood-brain barrier. At this point, the astrocytes begin to secrete a protein called MCP-1 that promotes inflammation. […] Both of these methods resulted in a delay in the spread of metastases. „These treatments succeeded in delaying the penetration of the cancer cells into the brain and their subsequent spread throughout the brain,” says Professor Satchi-Fainaro. […] It’s important to note that melanoma metastases in the brain are very aggressive with a poor prognosis of 15 months following surgery, radiation and chemotherapy.

• #52 The role of viruses in the pathogenesis of skin cancer in patients with chronic kidney disease and kidney transplant recipients | Musialik | Renal Disease and Transplantation Forum

  https://journals.viamedica.pl/renal_disease_and_transplant/article/view/104115

  In patients with chronic kidney disease and after kidney transplantation, the risk of cancer increases significantly due to the impaired function of the immune system. […] It was found that in both groups of patients the most common type of cancer are non-melanoma skin cancers and among them squamous cell carcinoma (sSCC). […] Viruses remain the key carcinogens in both sSCC and other primary skin cancers.

• #53 Risks and causes | Skin cancer | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/skin-cancer/risks-causes

  Your skin cannot repair damage from the sun if you have this condition. You should avoid all sun exposure and other sources of UV light. People with this condition often get skin cancers on exposed skin. […] Human papilloma virus (HPV) plays an important part in the development of skin cancer. […] Bowen’s disease is a very early form of skin cancer. Rarely, it can develop in the genital area. Research into this condition has shown that infection with HPV can increase the risk of developing Bowen’s disease. […] Some occupations and working with particular chemicals can increase your risk of skin cancer.

• #54 Risks and causes | Skin cancer | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/skin-cancer/risks-causes

  Sunbeds produce ultraviolet light which damages the skin. Research has shown that using a sunbed causes melanoma. There is now evidence to say that sunbeds might increase the risk of non melanoma skin cancer. […] People who have already had a skin cancer have a greater risk of getting another one compared to someone who hasn’t had one. Researchers think this is most likely because of sun exposure. […] You have an increased risk of developing a squamous cell skin cancer (SCC) if one of your parents has had a SCC. People who have a family history of melanoma have an increased risk of basal cell skin cancer (BCC). […] People with certain skin conditions can be more likely to develop skin cancer. […] Solar keratosis is a sign that your skin has already been damaged and you should take extra care to cover up in the sun. Over time it can turn into a squamous cell skin cancer, but this does not happen in everyone.

• #55

  https://journals.lww.com/melanomaresearch/fulltext/2010/06001/the_pathogenesis_of_skin_cancer_in_the.50.aspx

  Although the origin of post-transplant skin cancer is multifactorial, immunosuppressive treatments play a key role in most cases, and trigger the special clinical and progressive aspects observed in OTRs. […] All immunosuppressants allow cancer growth while inducing a decrease of immunosurveillance. […] In summary, all immunosuppressive agents contribute to skin cancer formation in OTRs. […] Current evidence, however, suggests that inflammation may be a double-edged sword. […] Nevertheless, the findings from several current and pre-publication studies are relevant to SCC, suggesting that a chronic smouldering inflammation may well contribute to tumour formation in SCC. […] If research bears out the suspicion that low-grade inflammation may drive carcinogenesis, then anti-inflammatory agents may prove helpful in preventing SCC development.

• #56 Chronic Inflammation Can Trigger Cancers Via Newly Discovered Mechanism | UCSF Helen Diller Family Comprehensive Cancer Center

  https://cancer.ucsf.edu/news/2018/08/23/chronic-inflammation-can-trigger-cancers-via-newly-discovered-mechanism

  It is well known that extended exposure to the suns UV rays can cause DNA mutations that lead to skin cancer. […] Now new research reveals that inflammation from chronic skin injury can trigger cancer-causing mutations as well by a totally distinct mechanism. […] Were describing for the first time a mechanism that instigates tissue damage-driven cancers, said study senior author Andrew South, PhD, an associate professor in the Department of Dermatology and Cutaneous Biology at Jefferson. […] The reason these patients get cancer is not well understood, but we realized that it had to be directly linked to chronic tissue damage, because the fragility of the skin is at the root of everything in this disease. […] Rather than focus on a few cancer-linked genes, the researchers sequenced the entire protein-coding part of the genome in these samples, which enabled them to detect subtle patterns of DNA mutation across the genome in inflamed and cancerous tissue that were clearly distinct from the types of mutational signatures caused by UV radiation.

• #57 The role of immune metabolism in skin cancers: implications for pathogenesis and therapy – Lu – Translational Cancer Research

  https://tcr.amegroups.org/article/view/88815/html

  Moreover, many carcinogenic environmental factors, such as ultraviolet (UV) radiation, can significantly impact the metabolic reprogramming of skin cells, contributing to the development and progression of skin cancers. […] Metabolic reprogramming is a hallmark of cancer cells, and skin cancers, such as melanoma and squamous cell carcinoma (SCC), are no exception. Tumor cells often exhibit increased glycolysis (the Warburg effect) and glutamine metabolism to support their rapid growth and proliferation. […] The metabolic reprogramming in melanoma cells not only supports their own growth but also influences the function of infiltrating immune cells. […] In summary, metabolic reprogramming is a key driver of skin cancer pathogenesis, contributing to tumor growth, metastasis, and immune evasion. By understanding the specific metabolic vulnerabilities of skin cancer cells and their associated immune cells, we can develop novel therapeutic strategies that target the metabolic basis of these diseases.

• #58 Advances in Pathogenesis and Treatment of Skin Cancer

  https://www.mdpi.com/1422-0067/26/3/1255

  Advances in Pathogenesis and Treatment of Skin Cancer […] The incidence of melanoma and non-melanoma skin cancers is steadily increasing, representing a significant public health concern. […] Intermittent exposure to ultraviolet radiation (UVR) and childhood sunburn are important pathogenetic factors for this neoplasm, especially in subjects with a fair complexion. […] Hereditary predisposition is another risk factor for melanoma. Several high-penetrance genes such as CDKN2A, CDK4, and BAP1 are the most commonly mutated in hereditary melanoma. […] The synthesis of a good photoprotective pigment, eumelanin, is recognized as a guarantee of photoprotection. […] The Rho/MRTF-A pathway has been shown to play a key role in drug resistance in human melanoma. […] There is increasing evidence that the pathogenesis of melanoma is also associated with specific aberrant epigenetic modifications that lead to drug resistance, immune evasion, apoptosis, and increased metastatic potential.

• #59 Advances in Pathogenesis and Treatment of Skin Cancer

  https://www.mdpi.com/1422-0067/26/3/1255

  An important target for epigenetic therapy in melanoma is EZH2, which is involved in disease progression by negatively regulating a number of tumor suppressor genes involved in cell transformation, proliferation, senescence escape, and apoptosis. […] The review by Nicoletti and co-workers highlights the existing research supporting the theory of a possible link between the pathogenesis of basal cell carcinoma (BCC) and a dysembryogenic process, with a particular focus on the Hedgehog signaling pathway, which is crucial for embryonic development.

• #60 Scientists identify key mechanism in development of skin cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2024/11/241122130626.htm

  LMU researchers have discovered how the interplay between a key protein and an endolysosomal ion channel promotes tumor development in skin cancer. […] A team led by LMU pharmacologist Professor Christian Grimm and Dr. Karin Bartel has now investigated the molecular mechanisms of tumorigenesis. […] As the researchers demonstrate, the interplay of two proteins — the ion channel TPC2 and the enzyme Rab7a — plays a decisive role, as they promote the growth and metastasis of melanoma. […] The ion channel controls the breakdown of important proteins in endolysosomes — cell organelles that are involved in transport and degradation processes — and thus influences signaling pathways that regulate tumor growth. […] Using modern methods such as endolysosomal patch-clamp electrophysiology and the measurement of lysosomal calcium release via fluorescence microscopy, the researchers established that there was indeed an interaction between Rab7a and TPC2 at the functional level, which promoted the growth and invasiveness of melanoma cells.

• #61 Scientists identify key mechanism in development of skin cancer | ScienceDaily

  https://www.sciencedaily.com/releases/2024/11/241122130626.htm

  „Our results show that Rab7a, by amplifying TPC2 activity, plays a key role in the regulation of tumor growth,” says Grimm. […] A particularly notable finding, according to the researchers, was that effects of the interaction of Rab7a and TPC2 could be demonstrated in vivo. […] „The interaction between Rab7a and TPC2 could pave the way for new therapeutic strategies which target the specific signaling pathways that promote melanoma growth and metastasis” concludes Grimm.

• #62 Scientists identify key mechanism in development of skin cancer – TheSynapse

  https://thesynapse.net/scientists-identify-key-mechanism-in-development-of-skin-cancer/

  Our results show that Rab7a, by amplifying TPC2 activity, plays a key role in the regulation of tumor growth, says Grimm. […] Specifically, the activation of TPC2 by Rab7a reduces the levels of a certain protein. This protein boosts the stability of a transcription factor that is a key regulator in melanocytes and melanomas and promotes their proliferation and survival. […] The interaction between Rab7a and TPC2 could pave the way for new therapeutic strategies which target the specific signaling pathways that promote melanoma growth and metastasis concludes Grimm.

• #63 Researchers reveal new mechanism behind skin cancer metastasis – SciLifeLab

  https://www.scilifelab.se/news/researchers-reveal-new-mechanism-behind-skin-cancer-metastasis/

  Creating drugs that can inhibit this signaling pathway could potentially be used to effectively treat squamous cell cancer. […] Since squamous cell cancer is similar to many other types of cancers, we believe that our findings can increase the understanding of these cancers as well, leading to the investigation of new drug targets, says Kim Thrane. […] The combination of these two methods helped us solve the puzzle of what cell types are in the tumor, what they do, where they are, and which cells they communicate with, says Kim Thrane.

• #64 Molecular Mechanisms and Biomarkers of Skin Photocarcinogenesis | IntechOpen

  https://www.intechopen.com/chapters/57023

  Past studies on UV radiation in skin carcinogenesis have identified at least three pathways involved in skin cancer development: genetic mutations, epigenetic changes and alterations in gene expression. […] Dysregulation of proto-oncogenes and tumor suppressor genes, which are critical for controlling cellular growth, is the mechanistic basis of cancer development. […] In skin cancer, many mutations in p53 are characterized by the CT and CCTT transitions, which are characteristic of the UV mutational signature. […] Mutations in the PTCH gene were initially detected in patients suffering from basal cell nevus syndrome. […] Aberrations in the HH signaling pathway are now recognized as major contributors in BCC tumorigenesis. […] Increasing evidence suggests that the underlying pathogenesis of cutaneous SCC involves mutations in several genes and pathways.

• #65

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/10000/a_recent_update_on_the_connection_between_dietary.33.aspx

  The CDKN2A gene encodes two proteins, p16INK4a and p14ARF, which act as tumor suppressors by regulating cell growth and division. […] Mutations in CDKN2A are commonly found in melanoma and can lead to the uncontrolled growth of melanocytes and the development of tumors. […] The TP53 gene encodes the tumor suppressor protein p53, which regulates cell growth, division, and apoptosis. […] Dietary phytochemicals are naturally occurring compounds found in plant-based foods, including fruits, vegetables, whole grains, nuts, seeds, and herbs. […] The health benefits of dietary phytochemicals are believed to come from their ability to interact with cellular signaling pathways, enzymes, and other molecules in the body, thereby modulating various biological processes. […] Overall, skin cancer therapy via diet-based phytochemicals is a promising approach for the prevention and treatment of skin cancer. […] The goal of this review article is to give a basic understanding of phytochemicals in the context of diet by describing their most important sources, chemical classes, and ability to prevent skin cancer.

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