Interaction of molecular alterations with immune response in melanoma

Abstract

Major advances have been made in melanoma treatment with the use of molecularly targeted therapies and immunotherapies, and numerous regimens are now approved by the US Food and Drug Administration for patients with stage IV disease. However, therapeutic resistance remains an issue to both classes of agents, and reliable biomarkers of therapeutic response and resistance are lacking. Mechanistic insights are being gained through preclinical studies and translational research, offering potential strategies to enhance responses and survival in treated patients. A comprehensive understanding of the immune effects of common mutations at play in melanoma is critical, as is an appreciation of the molecular mechanisms contributing to therapeutic resistance to immunotherapy. These mechanisms and the interplay between them are discussed herein. Cancer 2017;123:2130-42. © 2017 American Cancer Society.

Keywords: B-Raf proto-oncogene serine/threonine kinase (BRAF); catenin-β 1 (CTNNB1); combination therapy; guanosine-triphosphate guanyltransferase (GTPase); immunotherapy; melanoma; neoantigen; neuroblastoma rat sarcoma viral oncogene homolog (NRAS); personalized medicine; phosphatase and tensin homolog (PTEN); targeted therapy.