Presence of a BRAF c.1799T>A, p.Val600Glu (V600E) mutation in a microsatellite unstable colorectal carcinoma indicates that the tumor is probably sporadic and not associated with Lynch syndrome (HNPCC). However, if a BRAF mutation is not detected, the tumor may either be sporadic or Lynch syndrome associated. Detection of BRAF mutations may also be useful in determining patient eligibility for anti-EGFR treatment. Approximately 8--15% of colorectal cancer (CRC) tumors harbor BRAF mutations. The presence of BRAF mutation is significantly associated with right-sided colon cancers and is associated with decreased overall survival. Some studies have reported that patients with metastatic CRC (mCRC) that harbor BRAF mutations do not respond to anti-EGFR antibody agents cetuximab or panitumumab in the chemotherapy-refractory setting. BRAF V600-mutated CRCs may not be sensitive to V600E targeted TKIs. Drug: Vemurafenib + Panitumumab, Encorafenib + Binimetinib + Cetuximab, Radiation + Trametinib + Fluorouracil

B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. BRAF mutations are present in approximately 50% to 60% of cutaneous melanomas and are also present at lower frequencies in other melanoma subtypes. The hotspot for mutations in BRAF is at codon Val600 and the most common one is p.Val600Glu (V600E). Various B-Raf inhibitors(Vemurafenib, Dabrafenib) have been FDA approved for melanoma therapy in certain settings. Drug: Vemurafenib Dabrafenib Dabrafenib + Trametinib Vemurafenib + Cobimetinib Trametinib

Somatic mutations in BRAF have been found in 1-4% of all NSCLC most of which are adenocarcinomas and may be a potential therapeutic target in some settings. Drug: Vemurafenib, Dabrafenib, Dabrafenib + Trametinib

Vemurafenib Dabrafenib Dabrafenib + Trametinib Vemurafenib + Cobimetinib Vemurafenib + Panitumumab Encorafenib + Binimetinib + Cetuximab Radiation + Trametinib + Fluorouracil