[BRAF-Mutant Solid Tumor]

BRAF is a serine/threonine kinase that functions as a key component of the RAS/RAF/MEK/ERK (MAPK) signaling pathway and is recognized as an important oncogenic driver across multiple cancers. BRAF mutations are detected in a variety of malignancies including melanoma, thyroid cancer, colorectal cancer, non-small cell lung cancer, and biliary tract cancer. Among them, the V600 mutation results in constitutive activation of the MAPK pathway and promotes tumor growth and survival. BRAF mutations are currently classified into three functional classes (class 1-3) according to their signaling mechanisms and dependency on RAS activation. The development of BRAF inhibitors and MEK inhibitors has significantly improved outcomes in patients with BRAF V600-mutant melanoma, and combination therapy with these agents has become the standard of care. Clinical activity of BRAF/MEK inhibition has also been demonstrated in other malignancies such as non-small cell lung cancer and thyroid cancer. In contrast, BRAF-mutated colorectal cancer shows limited sensitivity to BRAF inhibitor monotherapy due to feedback activation of EGFR signaling, leading to the development of combination strategies including EGFR inhibitors. In recent years, basket trials such as VE-BASKET, NCI-MATCH, and ROAR have demonstrated the efficacy of BRAF-targeted therapies across tumor types, supporting the concept of tumor-agnostic treatment. Current BRAF inhibitors mainly target the active BRAF monomer; however, resistance mediated by RAF dimerization frequently occurs. Novel therapeutic approaches including pan-RAF inhibitors and ERK inhibitors are under development to overcome these resistance mechanisms.