[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-433009-105":59,"doc-detail-433009-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","melanoma-pathogenesis-and-targeted-therapy","Melanoma: Pathogenesis and Targeted Therapy","","Melanoma is the most aggressive skin malignant tumor, characterized by high mutation burden and frequently driven by alterations in NRAS, BRAF, or NF1. Targeted therapy can convert driver mutations into meaningful antitumor activity. Over the past decade, combined BRAF and MEK inhibition substantially improved outcomes for BRAF-mutant disease, while NRAS-mutant melanoma remains difficult to target. Recent MEK inhibitors, including binimetinib and tunlametinib, show efficacy in NRASmut melanoma, with tunlametinib as the first approved option for advanced NRASmut cases. Immune checkpoint inhibitors further reshaped treatment for advanced melanoma. This review summarizes molecular pathogenesis, classification, and current and potential therapeutic strategies, emphasizing clinical relevance and key challenges in both immunotherapy and targeted therapy.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/melanoma-pathogenesis-and-targeted-therapy/433009/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/melanoma-pathogenesis-and-targeted-therapy/433009.png","ImageObject",300,407,{"name":92,"@type":93},"SANS","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Which genetic alterations are most relevant to melanoma pathogenesis and targeted therapy?","Question",{"text":113,"@type":114},"Melanoma often involves driver alterations including NRAS, BRAF, and NF1. These can be exploited by targeted therapy to achieve antitumor activity.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How have BRAF inhibitors and MEK inhibitors changed outcomes for BRAF-mutant melanoma?",{"text":118,"@type":114},"In BRAF-mutant melanoma, BRAF inhibitors combined with MEK inhibitors have significantly improved prognosis compared with BRAF inhibition alone. This combination has become the current standard approach.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is NRAS-mutant melanoma considered difficult to target, and what treatment options exist?",{"text":122,"@type":114},"NRAS-mutant melanoma has been considered untargetable, with researchers exploring multiple strategies to interfere with NRAS signaling. MEK inhibitors have shown efficacy, and tunlametinib is the first and only approved MEK inhibitor for advanced NRASmut melanoma.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},433009,1790812023,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},962090760505,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","MedComm  \nREVIEW   \nMelanoma: Pathogenesis and Targeted Therapy  \nYang Fu  Jie Liu  Zeming Mo  Bin Wang  Yaotiao Deng  Yu Jiang  \nDepartment of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China Correspondence: Yaotiao Deng ([dengyaotiao@163.com](dengyaotiao@163.com))  Yu Jiang (jiang_yu@scu.edu.cn)  \nReceived: 2 September 2024  Revised: 2 December 2025  Accepted: 3 December 2025  \nKeywords: BRAF | immunotherapy | melanoma | NRAS | targeted therapy  \nABSTRACT  \nMelanoma is the most aggressive skin malignant tumor, typically exhibiting a high mutation burden and potentially harboring mutations in NRAS, BRAF, or NF1 . To enhance survival rates, these driver alterations can achieve significant antitumor activity through targeted therapy. In the past decade, BRAF inhibitors combined with MEK inhibitors significantly improved the prognosis of BRAF mutation melanoma. Nevertheless, researchers have attempted various strategies to block the NRAS signaling pathway, NRAS mutation in melanoma is still considered to be untargetable. In recent years, MEK inhibitors like binimetinib and tunlametinib have displayed the efficacy for NRASmut melanoma, with tunlametinib being the first and only approved MEK inhibitor for advanced NRASmut melanoma. On the other hand, immune checkpoint inhibitors including PD-1/PD-L1 inhibitors and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors changed the treatment landscape of advanced melanoma. In this review, we have summarized the current knowledge of molecular pathogenesis and classification of melanoma. Subsequently, we explored current and potential treatment approaches for melanoma, primarily encompassing BRAF inhibitors, MEK inhibitors, and immunotherapy, with a particular focus on their clinical relevance of development. Finally, the challenges in the treatment of melanoma, particularly in immunotherapy and targeted therapy, are summarized and discussed.  \n1  Introduction  \nMelanoma is a highly aggressive malignant tumor, which is derived from normal melanocytes. Over 280,000 cases (1.6%) of all newly diagnosed primary malignant cancers are cutaneous melanoma, and there are approximately 60,000 cancer deaths (0 .6% of cancer deaths) due to cutaneous melanoma in the world [1, 2] . The incidence of melanoma varies across different regions, with Southeast Asia reporting a lower incidence rate of 0.2 per 100,000 person-years compared with New Zealand (35.8 per 100,000 person-years), Australia (34.8 per 100,000 person-years), the EU (13.8 per 100,000 person-years), and the United States (7.7 per 100,000 person-years) [3] . In recent decades, 5-year survival rate of nonmetastatic melanoma has significantly improved due to the improvement of diagnosis, screening approaches, surgery,  \nand novel drugs. However, the prognosis of distant metastasis melanoma is still low, with a 5-year survival rate of about 27%[4, 5] .  \nCaucasians in Western countries mainly suffer from cutaneous melanoma, and ultraviolet exposure was recognized as a crucial factor in its etiology [6] . Nevertheless, non-Caucasians populations in Asia and Africa predominantly develop acral melanomas, which accounts for nearly 60% of all diagnosed melanoma cases in these areas [6, 7] . In addition, acral melanomas account for around 45% of melanoma cases in Chinese population [8] . The etiology of acral melanoma inAsia is still uncertain, although risk factors such as injury and mechanical stress of the feet/hands and chronic inflammation have been considered [7, 9, 10] . Mucosal melanoma is a rare subtype (1–2%) of melanomas in Caucasians  \n\n| Yang Fu, Jie Liu contributed equally to this work.\u003Cbr>|\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.\u003Cbr>© 2026 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion","cbCaiuSN1Ur793US","https://ap.wps.com/l/cbCaiuSN1Ur793US","pdf",3727297,39,"English","# Introduction\n# Melanoma Epidemiology and Subtypes\n## Cutaneous melanoma and risk factors\n## Acral and mucosal melanoma\n## Uveal melanoma\n# Oncogenic Drivers and Targeted Therapy\n## BRAF mutations and BRAF/MEK combinations\n## NRAS mutations and MEK inhibitor strategies\n# Immunotherapy for Advanced Melanoma\n## PD-1/PD-L1 and CTLA-4 inhibitors\n# Review Scope and Challenges","[{\"question\":\"Which genetic alterations are most relevant to melanoma pathogenesis and targeted therapy?\",\"answer\":\"Melanoma often involves driver alterations including NRAS, BRAF, and NF1. These can be exploited by targeted therapy to achieve antitumor activity.\"},{\"question\":\"How have BRAF inhibitors and MEK inhibitors changed outcomes for BRAF-mutant melanoma?\",\"answer\":\"In BRAF-mutant melanoma, BRAF inhibitors combined with MEK inhibitors have significantly improved prognosis compared with BRAF inhibition alone. This combination has become the current standard approach.\"},{\"question\":\"Why is NRAS-mutant melanoma considered difficult to target, and what treatment options exist?\",\"answer\":\"NRAS-mutant melanoma has been considered untargetable, with researchers exploring multiple strategies to interfere with NRAS signaling. MEK inhibitors have shown efficacy, and tunlametinib is the first and only approved MEK inhibitor for advanced NRASmut melanoma.\"}]","Melanoma: Pathogenesis and Targeted Therapy | PDF",1790662307,98]