Pharmacogenetics of BRAF in melanoma: mechanisms of drug resistance and therapeutic optimization – a systematic review

Abstract

   Background: Melanoma is the most lethal form of skin cancer with the highest mortality rate.
   Objective: To review research directions in pharmacogenetics related to the BRAF gene in melanoma.
   Methods: Data were extracted from three databases (PubMed, The Cochrane Library, and Science Direct) for studies published between January 2017 and December 2024, focusing on pharmacogenetics and the role of the BRAF gene in melanoma treatment.
   Results: Three main research directions were identified: (1) Elucidating mechanisms of drug resistance in BRAF-mutant patients, including NRAS/MEK mutations, PTEN loss, and drug transporter gene variants; (2) Utilizing genetic biomarkers (e.g., PD-L1) and combining targeted therapy with immunotherapy to enhance treatment efficacy; (3) Applying next-generation sequencing (NGS) for mutation detection and treatment regimen personalization.
   Conclusion: Clarifying drug resistance mechanisms, optimizing combination therapies, and integrating genetic technologies will contribute to improved treatment outcomes for BRAF-mutant melanoma.

DOI: 10.59715/pntjmp.5.2.2