Searching for the Chokehold of NRAS Mutant Melanoma

J Invest Dermatol. 2016 Jul;136(7):1330-1336. doi: 10.1016/j.jid.2016.03.006. Epub 2016 May 7.

Abstract

Up to 18% of melanomas harbor mutations in the neuroblastoma rat-sarcoma homolog (NRAS). Yet, decades of research aimed to interfere with oncogenic RAS signaling have been largely disappointing and have not resulted in meaningful clinical outputs. Recent advances in disease modeling, structural biology, and an improved understanding of RAS cycling as well as RAS signaling networks have renewed hope for developing strategies to selectively block hyperactive RAS function. This review discusses direct and indirect blocking of activated RAS with a focus on current and potential future therapeutic approaches for NRAS mutant melanoma.

Publication types

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

MeSH terms

  • Allosteric Site
  • Animals
  • Antineoplastic Agents / therapeutic use
  • DNA Mutational Analysis
  • Drug Therapy, Combination / methods
  • GTP Phosphohydrolases / antagonists & inhibitors
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Genes, ras
  • Humans
  • Immune System
  • MAP Kinase Signaling System
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutant Proteins / antagonists & inhibitors
  • Mutant Proteins / metabolism*
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Membrane Proteins
  • Mutant Proteins
  • RNA, Small Interfering
  • GTP Phosphohydrolases
  • NRAS protein, human
  • ras Proteins