MEK inhibitors for the treatment of NRAS mutant melanoma

Drug Des Devel Ther. 2018 Aug 20:12:2553-2565. doi: 10.2147/DDDT.S131721. eCollection 2018.

Abstract

Melanoma is increasing rapidly in incidence and prevalence, especially in younger females and older males. Treatment options have expanded beyond high-dose interleukin 2 and adoptive T-cell therapy to include inhibitors of immune checkpoints programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and small molecular inhibitors of pathways activated in melanoma, in particular the mitogen-activated protein kinase (MAPK) pathway. PD-1/CTLA-4 inhibitors and inhibitors of MAPK such as BRAF/MEK inhibitors have significantly improved survival in both the metastatic and, more recently, adjuvant settings. In this review, we discuss the preclinical data, clinical development, and potential use of novel MEK inhibitor binemetinib, particularly in the setting of NRAS mutant melanoma.

Keywords: BRAF; ERK; MAPK; MEK; NRAS; advanced; binimetinib; melanoma; metastatic.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / enzymology
  • Melanoma / genetics
  • Melanoma / pathology
  • Membrane Proteins / genetics*
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Molecular Targeted Therapy
  • Mutation*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Membrane Proteins
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase Kinases
  • GTP Phosphohydrolases
  • NRAS protein, human