{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:07:59Z","timestamp":1784203679549,"version":"3.55.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>BRAF V600E-mutant metastatic colorectal cancer (BRAF mCRC) is often associated with limited durable responses. After the publication of the randomized phase III BEACON trial investigating chemo-free regimens including BRAF inhibitors, anti-EGFR drugs, and MEK inhibitors (MEKis) in pre-treated BRAF mCRC patients, no MEKis have entered into clinical practice so far. Moreover, the recent phase III BREAKWATER trial investigating the first-line treatment of BRAF mCRC patients did not include MEKis at all. We present a compelling clinical case of a patient with BRAF mCRC who has experienced an extraordinary response to his MEKi-based treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>In 2019\u00a0a 60 years old male patient was diagnosed with BRAF mCRC (peritoneal metastases). The patient was asymptomatic, with PS 0. He was started on first-line treatment with FOLFOXIRI plus bevacizumab and after 8 cycles underwent curative surgery. One year later, due to peritoneal relapse, second-line treatment with the BRAF inhibitor vermurafenib combined to the MEKi cobimetinib was started within a phase II clinical trial. The patient has maintained stable disease with manageable side effects over nearly four years. He is still alive and in good clinical conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The prolonged progression-free survival seen in the present clinical case represents, to our knowledge, the longest documented response to a MEKi-based regimen in this setting, supporting the hypothesis that MEKis deserve reconsideration in mCRC treatment. This case highlights the value of personalized genomic profiling and practical clinical decision-making, offering insights into treatment sequencing, resistance mechanisms, and future targeted therapy strategies in BRAF mCRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1829831","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:43:52Z","timestamp":1784202232000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prolonged response to combined BRAF and MEK inhibition in BRAF mutant colorectal cancer, a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Michela","family":"Guardascione","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)","place":["Aviano, 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Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"de Scordilli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)","place":["Aviano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ongaro","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)","place":["Aviano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)","place":["Aviano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Calabr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS","place":["Aviano, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Botticelli","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome","place":["Rome, Italy"]},{"name":"Oncology Unit, Azienda Ospedaliero-Universitaria (AOU) Policlinico Umberto I","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Oncology, Istituto Dermopatico dell'Immacolata - Istituto di Ricovero e Cura a Carattere Scientifico (IDI - IRCCS)","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Puglisi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)","place":["Aviano, Italy"]},{"name":"Department of Medicine, University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26086","article-title":"Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer","volume":"117","author":"Tran","year":"2011","journal-title":"Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.01225","article-title":"Individual patient data meta-analysis of FOLFOXIRI plus bevacizumab versus doublets plus 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