Advanced Melanoma: Resistance Mechanisms to Current Therapies

Hematol Oncol Clin North Am. 2021 Feb;35(1):111-128. doi: 10.1016/j.hoc.2020.09.005. Epub 2020 Oct 26.

Abstract

Novel therapeutic agents introduced over the past decade, including immune checkpoint inhibitors and targeted therapies, have revolutionized the management of metastatic melanoma and significantly improved patient outcomes. Although robust and durable responses have been noted in some cases, treatment is often limited by innate or acquired resistance to these agents. This article provides an overview of known and suspected mechanisms involved with acquired resistance to BRAF/MEK inhibitors as well as developing insights into innate and acquired resistance to checkpoint inhibitors in patients with melanoma.

Keywords: BRAF inhibitor; Immune checkpoint inhibitor; Immunotherapy; MEK inhibitor; Melanoma; Resistance.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / physiology
  • Drug Resistance, Neoplasm* / genetics
  • Drug Resistance, Neoplasm* / immunology
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / immunology
  • Melanoma* / pathology
  • Microbiota / immunology
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf