{"entity":{"id":"braf-plus-mek","kind":"pairing","name":"BRAF inhibitor + MEK inhibitor","aka":[],"tldr":"Blocking two consecutive steps in the same relay prevents the pathway from rerouting and reduces side effects.","summary":"This combination pairs a BRAF inhibitor with a MEK inhibitor in the RAS / RAF / MEK / ERK (MAPK) pathway, blocking two consecutive steps of the same relay so the pathway cannot reroute. The mechanism is that BRAF inhibitor monotherapy causes paradoxical MEK and ERK reactivation through CRAF dimers, and adding MEK inhibition blocks that escape while reducing paradoxical MAPK activation and the skin cancers it produces. Dabrafenib plus trametinib and Encorafenib plus binimetinib improved progression-free and overall survival over a BRAF inhibitor alone in phase 3 Melanoma trials, and the combination has since gained a tumour-agnostic approval. It is used in Melanoma, Colorectal cancer and Non-small-cell lung cancer and serves as the template for vertical pathway inhibition.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT01909453: COLUMBUS","url":"https://clinicaltrials.gov/study/NCT01909453"}],"tags":[],"related":[],"cancers":["melanoma","colorectal","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["encorafenib"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"braf","b":"ras-mapk","rationale":"BRAF inhibitor monotherapy causes paradoxical MEK/ERK reactivation via CRAF dimers; adding MEK inhibition blocks the escape.","evidence":"Phase 3 OS benefit in melanoma; tumour-agnostic approval.","pairingType":"combination"},"route":"/pairings/braf-plus-mek/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"encorafenib","kind":"drug","name":"Encorafenib","route":"/drugs/encorafenib/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}]}}