{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:07:44Z","timestamp":1793362064715,"version":"4.5.0"},"reference-count":163,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>BRAF mutations are critical drivers in cancers such as melanoma, colorectal cancer, and non-small-cell lung cancer. The most common mutation, BRAF V600E, is a key therapeutic target. Targeted treatments with BRAF and MEK inhibitors have significantly improved progression-free and overall survival in melanoma patients. However, in cancers like metastatic colorectal cancer, BRAF mutations are associated with poor outcomes due to aggressive disease behavior and resistance to conventional chemotherapy. Despite progress, resistance to BRAF\/MEK inhibitors remains a major challenge, often driven by secondary mutations in the mitogen-activated protein kinase (MAPK) pathway, activation of alternative pathways such as phosphoinositide 3-kinases (PI3Ks)\/protein kinase B (AKT), or changes in the tumor microenvironment. These challenges have motivated ongoing research into combining BRAF inhibitors with immunotherapies to enhance and prolong treatment effectiveness. Future research must also account for the role of the cancer\u2019s tissue of origin, as the biological context significantly influences response to targeted therapies, highlighting the need for a deeper understanding of tumor biology, micro-environment, and genetics.<\/jats:p>","DOI":"10.3390\/ijms26083757","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T08:09:17Z","timestamp":1744790957000},"page":"3757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["BRAF Targeting Across Solid Tumors: Molecular Aspects and Clinical Applications"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9784-0333","authenticated-orcid":false,"given":"Hiba","family":"Mechahougui","sequence":"first","affiliation":[{"name":"Oncology Department, Geneva University Hospital (HUG), 1205 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9050-2267","authenticated-orcid":false,"given":"James","family":"Gutmans","sequence":"additional","affiliation":[{"name":"Oncology Department, Geneva University Hospital (HUG), 1205 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rouma\u00efssa","family":"Gouasmi","sequence":"additional","affiliation":[{"name":"Cancer Research Center of Lyon, CNRS UMR5286, Inserm U1052, University of Lyon, 69100 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Smekens","sequence":"additional","affiliation":[{"name":"Oncology Department, Geneva University Hospital (HUG), 1205 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Friedlaender","sequence":"additional","affiliation":[{"name":"Clinique G\u00e9n\u00e9rale Beaulieu, 1206 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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