Yiqun Zhang, Dawei Zhao, Di Wu
OPINION STATEMENT: Mucosal melanoma (MM) represents a rare malignancy in Caucasian populations but constitutes one of the predominant melanoma subtypes among non-Caucasian ethnic groups. Due to its anatomic occult nature, a significant proportion of patients with MM present with advanced-stage disease at diagnosis. Characterized by distinct genomic profiles and an immunosuppressive tumor microenvironment, MM exhibits suboptimal responses to current targeted drugs and immune checkpoint inhibitors (ICIs). Combination immunotherapy can overcome immune evasion by enhancing the infiltration of tumor-specific antigen-reactive T lymphocytes, thereby exhibiting potentiated anti-tumor activity. However, the rarity of MM has posed significant barriers to better understanding immunotherapy resistance mechanisms and investigating novel therapies. Consequently, there is a critical unmet need for establishing standardized treatment guidelines to improve survival outcomes in advanced MM. This article comprehensively reviews current status in the treatment of advanced MM. It also discusses potential future directions for treatment based on recent advances from clinical trials and basic research.