BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). Activating BRAF(V600E) (Val600Glu) mutations have been identified in approximately 1-2% of lung adenocarcinomas. Various BRAF inhibitors (Vemurafenib, Dabrafenib, and Trametinib) have been FDA approved for therapy for some tumor types in certain clinical settings. Of note, Dabrafenib and Trametinib are approved for metastatic non-small cell lung cancer (NSCLC) harboring BRAF V600E mutations.
Planchard D, et al. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(5):642-50
Flaherty KT, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012;367(2):107-14
Flaherty KT, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010;363(9):809-19
Gautschi O, et al. A patient with BRAF V600E lung adenocarcinoma responding to vemurafenib. J Thorac Oncol 2012;7(10):e23-4
Odogwu L, Mathieu L, Blumenthal G, Larkins E, Goldberg KB, Griffin N, Bijwaard K, Lee EY, Philip R, Jiang X, Rodriguez L, McKee AE, Keegan P, Pazdur R. FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non-Small Cell Lung Cancers Harboring BRAF V600E Mutations. Oncologist. 2018 Jun;23(6):740-745.
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