Combinatorial Approaches to the Treatment of Advanced Melanoma

Hematol Oncol Clin North Am. 2021 Feb;35(1):145-158. doi: 10.1016/j.hoc.2020.08.015. Epub 2020 Oct 26.

Abstract

The treatment landscape for patients with advanced melanoma has dramatically improved over the past decade, leading to unprecedented survival. Despite the robust activity of single-agent immune-checkpoint blockade with anti-CTLA-4 or anti-PD-1 agents, and the efficacy of targeted therapies capable of interrupting aberrant signaling resulting from BRAF mutations, the benefit from these therapies is not universal. Advanced understanding of immune and molecular processes underlying melanoma tumorigenesis has demonstrated the promise of combined, multidrug regimens. We discuss the currently available evidence that supports using combinatorial approaches in advanced melanoma treatment and provide insights into promising new combination strategies under investigation.

Keywords: BRAF; Immunotherapy; MAPK; Melanoma.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Drug Therapy, Combination / methods*
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / pathology
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors

Substances

  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors
  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases