{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:17:51Z","timestamp":1785860271648,"version":"3.56.0"},"reference-count":99,"publisher":"OAE Publishing Inc.","content-domain":{"domain":["oaepublish.com"],"crossmark-restriction":false},"short-container-title":["Cancer Drug Resist."],"abstract":"<jats:p>Aim:  As intrinsic resistance - often driven by concurrent genomic alterations in tumor suppressor genes or oncogenes - remains a major challenge in oncology, this work aimed to comprehensively analyze BRAF  somatic alterations across cancer types and identify new potential therapeutic strategies to overcome drug resistance.<\/jats:p>\n          <jats:p>Methods:  We conducted an extensive analysis of genomics, transcriptomics, and clinical data retrieved from public repositories, including cBioPortal. Our comprehensive analysis examined BRAF  alterations [point mutations, structural variants (SVs) and copy number alteration] in more than 217,000 tumor samples across 120 distinct tumor types from primary and metastatic sites in both adult and pediatric cohorts, focusing on mutual exclusivity and co-occurrence of mutations in other oncogenes or tumor suppressors. The work also explores the association of BRAF  somatic alterations with survival, clinical and molecular features.<\/jats:p>\n          <jats:p>Results:  Analysis of mutation frequencies across cancer types revealed that BRAFV600E represents approximately 90% of all BRAF  alterations. While melanoma and thyroid carcinoma show the highest prevalence of BRAF  mutations, followed by colorectal and non-small cell lung cancer in terms of absolute number of patients harboring BRAF  mutations worldwide, notably high mutation frequencies were identified in rare malignancies, including hairy-cell leukemia, ganglioglioma, and serous borderline ovarian tumors. The comprehensive analysis of genomic profiling data across these tumors uncovered distinct patterns of co-occurring and mutually exclusive alterations in oncogenes and tumor suppressor genes, illuminating resistance mechanisms and suggesting novel therapeutic combinations.<\/jats:p>\n          <jats:p>Conclusion:  Comprehensive genomic profiling is critical for optimizing targeted therapy and overcoming drug resistance in BRAF -mutated cancers. The identification of co-occurring alterations provides opportunities for rational combination therapies, emphasizing the importance of detailed mutation profiling in developing effective treatment strategies across diverse cancer types.<\/jats:p>","DOI":"10.20517\/cdr.2024.213","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T10:18:14Z","timestamp":1742811494000},"update-policy":"https:\/\/doi.org\/10.20517\/oae.crossmark.policy","source":"Crossref","is-referenced-by-count":3,"title":["Unraveling <i>BRAF<\/i> alterations: molecular insights to circumvent therapeutic resistance across cancer types"],"prefix":"10.20517","author":[{"given":"Caterina","family":"Perfetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Aprile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Cataldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Giovannetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"8410","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c00332"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/genes11111342"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.mct-10-0799"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02282-2"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.11.018"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.05.037"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-13-0440"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/pat.0b013e328360b61d"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26086"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature23291"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0171-x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081197"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2954"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203980"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022769"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4750"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-0816"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-12-0095"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1406498"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3692"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902651116"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nature11125"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1200\/po.16.00054"},{"key":"B28","unstructured":"Battaglin F, Naseem M, Lenz HJ, Salem ME. 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