[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-374134-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-374134-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","advances-in-pathogenesis-and-treatment-of-skin-cancer","Advances in Pathogenesis and Treatment of Skin Cancer","","Special Issue editorial on skin cancers emphasizes etiopathogenesis and the most innovative, effective therapies. It highlights rising incidence of melanoma and non-melanoma skin cancer as a major public health concern and reviews key pathogenetic drivers, including ultraviolet exposure, hereditary susceptibility, and pigmentation factors. It summarizes mechanistic insights on MC1R variants and acral melanoma, then contrasts treatment strategies across surgery, BRAF/MEK targeted therapy, relapse limitations, and immunotherapy outcomes, including future adjuvant and combination directions.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/advances-in-pathogenesis-and-treatment-of-skin-cancer/374134/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/advances-in-pathogenesis-and-treatment-of-skin-cancer/374134.png","ImageObject",300,407,{"name":42,"@type":43},"Ivy","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",19,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What risk factors are highlighted for melanoma development?","Question",{"text":63,"@type":64},"Intermittent ultraviolet radiation exposure and childhood sunburn are described as important pathogenetic factors, particularly in individuals with fair complexion. Hereditary predisposition and pigmentation-related factors involving melanin and MC1R variants are also emphasized.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do MC1R polymorphic variants relate to melanoma aggressiveness?",{"text":68,"@type":64},"The editorial notes studies using a melanoma model to compare transduction efficacy of red-hair-associated MC1R variants. Minimal residual cAMP-related activity is reported, while ERK pathway transduction is effective, linking MC1R functionality to increased aggressiveness and antioxidant self-defense.",{"name":70,"@type":61,"acceptedAnswer":71},"What treatment advances are discussed for metastatic melanoma?",{"text":72,"@type":64},"It contrasts molecular targeted BRAF/MEK inhibitor therapy with its limitations and relapses, then presents immunotherapy as a major turning point with substantial cure rates for metastatic melanoma. It also mentions ongoing exploration of combination and adjuvant agent strategies for future challenges.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},374134,1790816420,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":97,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","Editorial  \nAdvances in Pathogenesis and Treatment of Skin Cancer Enrica Flori , Giorgia Cardinali * and Vittoria Maresca  \nReceived: 15 January 2025  \nAccepted: 30 January 2025  \nPublished: 31 January 2025  \nCitation: Flori, E.; Cardinali, G.; Maresca, V. Advances in Pathogenesis and Treatment of Skin Cancer. Int. J.  \nMol. Sci. 2025, 26, 1255. [https://](https://)[ ](https://)[doi.org/10.3390/ijms26031255](doi.org/10.3390/ijms26031255)  \n[Copyright:](Copyright:) © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \nLaboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, Italy; enrica.flori@ifo.it (E.F.); vittoria.maresca@ifo.it (V.M.)  \n* Correspondence: [giorgia.cardinali@ifo.it](giorgia.cardinali@ifo.it)  \nThis Special Issue is a collection of papers on skin cancers, focusing on their etiopathogenesis and the most innovative and effective therapies. The incidence of melanoma and non-melanoma skin cancers is steadily increasing, representing a significant public health concern. In recent years, significant efforts have been made to develop effective therapeutic options, although many questions remain open.  \nGosman et al. [1] wrote a comprehensive review of the literature on cutaneous melanoma and its management. Intermittent exposure to ultraviolet radiation (UVR) and childhood sunburn are important pathogenetic factors for this neoplasm, especially in subjects with a fair complexion. Pale skin associated with a high number of nevi indicates the presence of a low level of melanin, the main physical and chemical filter against UVR. 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. Some medium-penetrance genes, such as MC1R, which encodes the alpha-melanocyte-stimulating hormone receptor, are also involved in inherited cutaneous melanoma. The synthesis of a good photoprotective pigment, eumelanin, is recognized asa guarantee of photoprotection. Red-haired individuals are often carriers of MC1R polymorphisms, commonly known as loss-of-function variants. The paper by Cerdido et al. [2] belongs to a research group that has consolidated experience in the biology of MC1R and its ligand, αMSH. The authors consider the attribute \"loss of function\" to be an inappropriate definition. The same research group previously described for the first time the ability of stimulated MC1R to activate mitogenic extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling [3] . ERK1/2 is the effector of the MAPK pathway, which is primarily involved in determining the aggressiveness of melanoma. Here, the authors present an interesting study using a human melanoma line to create a construct that allows the comparison of the transduction efficacy of two polymorphic variants of MC1R associated with the red hair phenotype. The authors demonstrate minimal residual activity concerning cAMP-related signaling, but highlight effective transduction for the ERK pathway. This result means that the functionality of MC1R in the presence of these polymorphic variants is an aggravating factor in melanoma, increasing its aggressiveness and antioxidant self-defense. Nevertheless, there are cutaneous melanomas, such as acral melanoma, that occur in unexposed areas of the skin. The review by Choi et al. [4] is very comprehensive in this respect. In fact, acral melanoma mainly occurs in dark-skinned individuals and is localized to non-photoexposed areas of the skin (palms and soles) . Acral melanoma is a challenge from a biological point of view because it is an extremely aggressi","cbCaijn4BaRjtMff","https://ap.wps.com/l/cbCaijn4BaRjtMff","pdf",190272,"English","# Editorial overview\n## Etiopathogenesis and risk factors\n## Molecular mechanisms and MC1R signaling\n## Acral melanoma and social challenges\n## Treatment evolution: surgery to targeted therapy\n## Immunotherapy and future directions","[{\"question\":\"What risk factors are highlighted for melanoma development?\",\"answer\":\"Intermittent ultraviolet radiation exposure and childhood sunburn are described as important pathogenetic factors, particularly in individuals with fair complexion. Hereditary predisposition and pigmentation-related factors involving melanin and MC1R variants are also emphasized.\"},{\"question\":\"How do MC1R polymorphic variants relate to melanoma aggressiveness?\",\"answer\":\"The editorial notes studies using a melanoma model to compare transduction efficacy of red-hair-associated MC1R variants. Minimal residual cAMP-related activity is reported, while ERK pathway transduction is effective, linking MC1R functionality to increased aggressiveness and antioxidant self-defense.\"},{\"question\":\"What treatment advances are discussed for metastatic melanoma?\",\"answer\":\"It contrasts molecular targeted BRAF/MEK inhibitor therapy with its limitations and relapses, then presents immunotherapy as a major turning point with substantial cure rates for metastatic melanoma. It also mentions ongoing exploration of combination and adjuvant agent strategies for future challenges.\"}]","Advances in Pathogenesis and Treatment of Skin Cancer | PDF",1790201186,13]