The mechanism and consequences of BRAF inhibitor resistance in melanoma

Abstract

BRAF ^V600E is a constitutive BRAF (B-raf proto-oncogene, serine/threonine kinase) mutation that accounts for more than 90% of BRAF mutations in melanoma. Vemurafenib is a BRAF ^V600E selective kinase inhibitor (BRAFi) that is commonly used to treat BRAF ^V600E melanoma patients. However, vemurafenib treatment-induced resistance occurs in about 50% of patients diagnosed with melanoma, and half of the patients have disease progression within six months. But the mechanism and the consequences of BRAF inhibitor resistance have not been fully elucidated. In this review, we summarize the mechanism and the consequences of BRAF inhibitor vemurafenib resistance in melanoma, aiming to provide a guidance for the intervention of BRAF inhibitor resistance.

Funding

National Natural Science Foundation of China(32260167); Yunnan Applied Basic Research Projects(202101AV070002); Key Laboratory of Tumor Immunological Prevention and Treatment in Yunnan Province, Yan'an Hospital Affiliated to Kunming Medical University(Grant No. KLTIPT-2023-02); Yunnan University(Grant No. 2023Y0222)