The role of targeted therapy for melanoma in the immunotherapy era

Over the past 10 years of remarkable development of both molecularly targeted and immune-targeted therapy for the treatment of melanoma, a clear preference of immunotherapy over molecularly targeted therapy has emerged among melanoma treatment providers. Still, the clinical data remain remarkable for patients with BRAFmutant stage III and IV melanoma, and there seems to be a clear benefit of BRAF-targeted therapy for these patients. The key, then, is to identify the best way to use BRAF-targeted therapy. In this review, the clinical data of molecular-targeted therapy are summarized, mechanisms of resistance to single-agent BRAF and combined BRAF with mitogenactivated protein kinase/extracellular signal-regulated kinase inhibitor are discussed, and strategies to overcome this resistance are presented; then, we review a number of clinical dilemmas that influence the decision-making of using targeted therapy over immunotherapy, and vice versa, and help define the specific role of targeted therapy in the immunotherapy era.With the fervor over the potential durable remissions associated with immunotherapy and the enhanced knowledge of cancer immunity, an immense amount of energy is being spent developing more effective single-agent and combination therapies.

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