Advances in the discovery and development of melanoma drug therapies

Expert Opin Drug Discov. 2021 Nov;16(11):1319-1347. doi: 10.1080/17460441.2021.1942834. Epub 2021 Jul 19.

Abstract

Introduction: Therapeutic strategies for melanoma have evolved significantly over the last decade shifting from cytotoxic chemotherapies like dacarbazine to targeted therapies and immunotherapies including immune checkpoint inhibitors. These new drug therapies have improved overall as well as progression-free survival, lowering the mortality of this cancer for melanoma patients with advanced disease. Newer strategies incorporate combination therapies that harness synergies between mechanisms of anticancer efficacy as well as help overcome resistance issues of monotherapies, which remain a challenge.

Areas covered: This review looks at each class of drug therapy for melanoma and provides an overview of the preclinical mechanism of action, the clinical efficacy data, and their applications in combination therapy regimens. NCCN treatment guidelines, safety, toxicity, and immune-related adverse events are also described as well as a note on cost.

Expert opinion: Numerous ongoing trials continue to evaluate the role of novel therapies and combinations for this challenging disease and understanding their mechanism of action, risks, benefits, and treatment guidelines can help care providers and patients have a more comprehensive and tailored discussion of treatment options and expectations.

Keywords: BRAF; MEK inhibitors; Melanoma; chemotherapy; clinical trials; immune checkpoint inhibitors; immunotherapy; targeted therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Combined Modality Therapy
  • Humans
  • Immunotherapy
  • Melanoma* / drug therapy
  • Molecular Targeted Therapy
  • Proto-Oncogene Proteins B-raf
  • Treatment Outcome

Substances

  • Proto-Oncogene Proteins B-raf