{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:18:15Z","timestamp":1788171495402,"version":"build-2803163510"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastrointest Canc"],"DOI":"10.1007\/s12029-026-01581-0","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:56:02Z","timestamp":1788170162000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BRAF V600E-Mutated Metastatic Colorectal Cancer: Practical Management in the Post-BREAKWATER Era"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1994-4795","authenticated-orcid":false,"given":"Tamotsu","family":"Sagawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koshi","family":"Fujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"6892","key":"1581_CR1","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/nature00766","volume":"417","author":"H Davies","year":"2002","unstructured":"Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949\u201354. https:\/\/doi.org\/10.1038\/nature00766.","journal-title":"Nature"},{"issue":"5","key":"1581_CR2","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/bjc.2011.19","volume":"104","author":"T Yokota","year":"2011","unstructured":"Yokota T, Ura T, Shibata N, Takahari D, Shitara K, Nomura M, et al. BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer. 2011;104(5):856\u201362. https:\/\/doi.org\/10.1038\/bjc.2011.19.","journal-title":"Br J Cancer"},{"issue":"11","key":"1581_CR3","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/nm.3967","volume":"21","author":"J Guinney","year":"2015","unstructured":"Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350\u20136. https:\/\/doi.org\/10.1038\/nm.3967.","journal-title":"Nat Med"},{"issue":"7387","key":"1581_CR4","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/nature10868","volume":"483","author":"A Prahallad","year":"2012","unstructured":"Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. 2012;483(7387):100\u20133. https:\/\/doi.org\/10.1038\/nature10868.","journal-title":"Nature"},{"issue":"17","key":"1581_CR5","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1056\/NEJMoa1908075","volume":"381","author":"S Kopetz","year":"2019","unstructured":"Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019;381(17):1632\u201343. https:\/\/doi.org\/10.1056\/NEJMoa1908075.","journal-title":"N Engl J Med"},{"issue":"4","key":"1581_CR6","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1200\/JCO.20.02088","volume":"39","author":"J Tabernero","year":"2021","unstructured":"Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol. 2021;39(4):273\u201384. https:\/\/doi.org\/10.1200\/JCO.20.02088.","journal-title":"J Clin Oncol"},{"issue":"24","key":"1581_CR7","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1056\/NEJMoa2501912","volume":"392","author":"E Elez","year":"2025","unstructured":"Elez E, Yoshino T, Shen L, Lonardi S, Van Cutsem E, Eng C, et al. Encorafenib, cetuximab, and mFOLFOX6 in BRAF-mutated colorectal cancer. N Engl J Med. 2025;392(24):2425\u201337. https:\/\/doi.org\/10.1056\/NEJMoa2501912.","journal-title":"N Engl J Med"},{"issue":"8","key":"1581_CR8","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1016\/j.annonc.2026.04.017","volume":"37","author":"S Kopetz","year":"2026","unstructured":"Kopetz S, Tabernero J, Lonardi S, et al. A randomised study of encorafenib, cetuximab, and FOLFIRI versus FOLFIRI with or without bevacizumab in BRAF V600E-mutant colorectal cancer: BREAKWATER Cohort 3. Ann Oncol. 2026;37(8):1133\u201343. https:\/\/doi.org\/10.1016\/j.annonc.2026.04.017.","journal-title":"Ann Oncol"},{"issue":"13","key":"1581_CR9","doi-asserted-by":"publisher","first-page":"3954","DOI":"10.1158\/1078-0432.CCR-19-0311","volume":"25","author":"M Schirripa","year":"2019","unstructured":"Schirripa M, Biason P, Lonardi S, Pella N, Pino MS, Urbano F, Cremolini C, et al. Class 1, 2, and 3 BRAF-mutated metastatic colorectal cancer: a detailed clinical, pathologic, and molecular characterization. Clin Cancer Res. 2019;25(13):3954\u201361. https:\/\/doi.org\/10.1158\/1078-0432.CCR-19-0311.","journal-title":"Clin Cancer Res"},{"issue":"6","key":"1581_CR10","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1158\/1078-0432.CCR-14-2779","volume":"21","author":"R Yaeger","year":"2015","unstructured":"Yaeger R, Cercek A, O\u2019Reilly EM, Reidy DL, Kemeny N, Wolinsky T, et al. Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic colorectal cancer patients. Clin Cancer Res. 2015;21(6):1313\u201320. https:\/\/doi.org\/10.1158\/1078-0432.CCR-14-2779.","journal-title":"Clin Cancer Res"},{"key":"1581_CR11","unstructured":"National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Colon Cancer. Version 2.2026. NCCN; 2026. Published April 7, 2026. Accessed July 1, 2026."},{"issue":"23","key":"1581_CR12","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","volume":"383","author":"T Andre","year":"2020","unstructured":"Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207\u201318. https:\/\/doi.org\/10.1056\/NEJMoa2017699.","journal-title":"N Engl J Med"},{"issue":"11","key":"1581_CR13","doi-asserted-by":"publisher","first-page":"653","DOI":"10.2217\/fon-2022-1249","volume":"20","author":"E Elez","year":"2024","unstructured":"Elez E, Kopetz S, Tabernero J, Bekaii-Saab T, Taieb J, Yoshino T, et al. SEAMARK: phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H\/dMMR BRAF V600E-mutant mCRC. Future Oncol. 2024;20(11):653\u201363. https:\/\/doi.org\/10.2217\/fon-2022-1249.","journal-title":"Future Oncol"},{"issue":"5","key":"1581_CR14","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/S1470-2045(22)00197-8","volume":"23","author":"LA Diaz Jr","year":"2022","unstructured":"Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022;23(5):659\u201370. https:\/\/doi.org\/10.1016\/S1470-2045(22)00197-8.","journal-title":"Lancet Oncol"},{"issue":"21","key":"1581_CR15","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1056\/NEJMoa2402141","volume":"391","author":"T Andre","year":"2024","unstructured":"Andre T, Elez E, Van Cutsem E, Kim TW, Deming DA, Yoshino T, et al. Nivolumab plus ipilimumab in microsatellite-instability-high metastatic colorectal cancer. N Engl J Med. 2024;391(21):2014\u201326. https:\/\/doi.org\/10.1056\/NEJMoa2402141.","journal-title":"N Engl J Med"},{"issue":"4","key":"1581_CR16","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1200\/JCO.20.01994","volume":"39","author":"S Kopetz","year":"2021","unstructured":"Kopetz S, Guthrie KA, Morris VK, Lenz HJ, Magliocco AM, Maru D, et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406). J Clin Oncol. 2021;39(4):285\u201394. https:\/\/doi.org\/10.1200\/JCO.20.01994.","journal-title":"J Clin Oncol"},{"issue":"14","key":"1581_CR17","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1200\/JCO.22.01693","volume":"41","author":"E Van Cutsem","year":"2023","unstructured":"Van Cutsem E, Taieb J, Yaeger R, Maiello E, Yoshino T, Elez E, et al. ANCHOR CRC: results from a single-arm, phase II study of encorafenib plus binimetinib and cetuximab in previously untreated BRAF V600E-mutant metastatic colorectal cancer. J Clin Oncol. 2023;41(14):2628\u201337. https:\/\/doi.org\/10.1200\/JCO.22.01693.","journal-title":"J Clin Oncol"},{"key":"1581_CR18","unstructured":"US Food and Drug Administration. FDA grants traditional approval to encorafenib for metastatic colorectal cancer with a BRAF V600E mutation. Published February 24. 2026. Accessed July 1, 2026."},{"issue":"12","key":"1581_CR19","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.1007\/s10147-025-02899-8","volume":"30","author":"Y Kinugasa","year":"2025","unstructured":"Kinugasa Y, Uehara K, Yamaguchi K, Saito Y, Murofushi K, Sugai T, et al. Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2024 for the treatment of colorectal cancer. Int J Clin Oncol. 2025;30(12):2410\u201363. https:\/\/doi.org\/10.1007\/s10147-025-02899-8.","journal-title":"Int J Clin Oncol"},{"key":"1581_CR20","unstructured":"Japanese Society for Cancer of the Colon and Rectum. Evidence to be added to the JSCCR Guidelines 2024 for the medical treatment of unresectable advanced\/recurrent colorectal cancer: encorafenib plus cetuximab plus mFOLFOX6 as first-line treatment for BRAF-mutated colorectal cancer. Published. December 2025. Accessed July 1, 2026."},{"key":"1581_CR21","unstructured":"European Society for Medical Oncology. ESMO Living Guideline: metastatic colorectal cancer, first-line therapy for metastatic colorectal cancer. Accessed July 1, 2026."},{"key":"1581_CR22","doi-asserted-by":"publisher","first-page":"115645","DOI":"10.1016\/j.ejca.2025.115645","volume":"227","author":"C Gallois","year":"2025","unstructured":"Gallois C, Ambrosini M, Lonardi S, Alouani E, Guimbaud R, Overman MJ, et al. Prognostic impact of the BRAF V600E mutation in patients with MSI-high metastatic colorectal cancer treated with immune checkpoint inhibitors. Eur J Cancer. 2025;227:115645. https:\/\/doi.org\/10.1016\/j.ejca.2025.115645.","journal-title":"Eur J Cancer"},{"issue":"6","key":"1581_CR23","doi-asserted-by":"publisher","first-page":"100603","DOI":"10.1016\/j.esmoop.2022.100603","volume":"7","author":"E Martinelli","year":"2022","unstructured":"Martinelli E, Cremolini C, Mazard T, et al. Real-world first-line treatment of patients with BRAF V600E-mutant metastatic colorectal cancer: the CAPSTAN CRC study. ESMO Open. 2022;7(6):100603. https:\/\/doi.org\/10.1016\/j.esmoop.2022.100603.","journal-title":"ESMO Open"},{"issue":"1","key":"1581_CR24","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s41416-024-02711-w","volume":"131","author":"K Zwart","year":"2024","unstructured":"Zwart K, van Nassau SCMW, Koopman M, Snaebjornsson P, van Gestel AJ, et al. Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab. Br J Cancer. 2024;131(1):110\u201316. https:\/\/doi.org\/10.1038\/s41416-024-02711-w.","journal-title":"Br J Cancer"},{"issue":"23","key":"1581_CR25","doi-asserted-by":"publisher","first-page":"6513","DOI":"10.1158\/0008-5472.CAN-17-0768","volume":"77","author":"R Yaeger","year":"2017","unstructured":"Yaeger R, Yao Z, Hyman DM, Hechtman JF, Vakiani E, Zhao HY, Su W, Wang L, Joelson A, Cercek A, et al. Mechanisms of acquired resistance to BRAF V600E inhibition in colon cancers converge on RAF dimerization and are sensitive to its inhibition. Cancer Res. 2017;77(23):6513\u201323. https:\/\/doi.org\/10.1158\/0008-5472.CAN-17-0768.","journal-title":"Cancer Res"},{"issue":"23","key":"1581_CR26","doi-asserted-by":"publisher","first-page":"2624","DOI":"10.1200\/JCO.2016.71.4394","volume":"35","author":"JC Jones","year":"2017","unstructured":"Jones JC, Renfro LA, Al-Shamsi HO, Schrock AB, Rankin A, Zhang BY, et al. Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer. J Clin Oncol. 2017;35(23):2624\u201330. https:\/\/doi.org\/10.1200\/JCO.2016.71.4394.","journal-title":"J Clin Oncol"}],"container-title":["Journal of Gastrointestinal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01581-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12029-026-01581-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12029-026-01581-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:56:04Z","timestamp":1788170164000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12029-026-01581-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1581"],"URL":"https:\/\/doi.org\/10.1007\/s12029-026-01581-0","relation":{},"ISSN":["1941-6636"],"issn-type":[{"value":"1941-6636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"13 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for Publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest related to this manuscript.","order":4,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":5,"name":"Ethics","label":"Clinical trial number","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"202"}}