Treatment of BRAF-mutated advanced cutaneous melanoma

The field of melanoma oncology has recently awakened with groundbreaking scientific advances and innovative therapeutic strategies. New groups of small-molecule kinase inhibitors targeting the aberrant mitogen-activated protein kinase (MAPK) pathway activation mediating tumor growth and survival have revolutionized the therapeutic approach to advanced melanoma. BRAF and MEK inhibitors are the first groups of agents that improved all clinical efficacy endpoints, including response rate, progression-free survival (PFS) and overall survival (OS), in patients with BRAF-mutated advanced melanoma when compared with standard chemotherapy in randomized phase III studies. However, despite the impressive clinical responses in patients with BRAF mutant advanced melanoma, duration of response to MAPK pathway-targeted therapy remains limited, implicating rapid emergence of drug resistance. Diverse strategies to overcome tumor resistance to MAPK inhibitors, the focus of today's translational and clinical research, will further improve the clinical outcome for patients with BRAF-mutated advanced melanoma in the near future.