Developments in the Space of New MAPK Pathway Inhibitors for BRAF-Mutant Melanoma

Clin Cancer Res. 2019 Oct 1;25(19):5735-5742. doi: 10.1158/1078-0432.CCR-18-0836. Epub 2019 Apr 16.

Abstract

The characterization of the MAPK signaling pathway has led to the development of multiple promising targeted therapy options for a subset of patients with metastatic melanoma. The combination of BRAF and MEK inhibitors represents an FDA-approved standard of care in patients with metastatic and resected BRAF-mutated melanoma. There are currently three FDA-approved BRAF/MEK inhibitor combinations for the treatment of patients with BRAF-mutated melanoma. Although there have been significant advances in the field of targeted therapy, further exploration of new targets within the MAPK pathway will strengthen therapeutic options for patients. Important clinical and translational research focuses on mechanisms of resistance, predictive biomarkers, and challenging patient populations such as those with brain metastases or resected melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • Molecular Targeted Therapy / methods
  • Mutation*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf