Roles and mechanisms of aberrant alternative splicing in melanoma — implications for targeted therapy and immunotherapy resistance

Despite advances in therapeutic strategies, resistance to immunotherapy and the off-target effects of targeted therapy have significantly weakened the benefits for patients with melanoma. Alternative splicing plays a crucial role in transcriptional reprogramming during melanoma development. In particular, aberrant alternative splicing is involved in the efficacy of immunotherapy, targeted therapy, and melanoma metastasis. Abnormal expression of splicing factors and variants may serve as biomarkers or therapeutic targets for the diagnosis and prognosis of melanoma. Therefore, comprehensively integrating their roles and related mechanisms is essential. This review provides the first detailed summary of the splicing process in melanoma and the changes occurring in this pathway. The focus of this review is to provide strategies for developing novel diagnostic biomarkers and summarize their potential to alter resistance to targeted therapies and immunotherapy.