ERK pathway inhibitors: how low should we go?

Cancer Discov. 2013 Jul;3(7):719-21. doi: 10.1158/2159-8290.CD-13-0245.

Abstract

Resistance to RAF inhibitors is generally accompanied by reactivation of extracellular signal-regulated kinase (ERK) signaling. SCH772984, a selective, ATP-competitive inhibitor of ERK1 and ERK2, is effective in BRAF-mutant models in which resistance is the result of ERK reactivation. SCH772984 may also have a role in the treatment of tumors in which ERK is dysregulated by mutant RAS, NF1, or activated receptor tyrosine kinases, settings in which current RAF inhibitors are ineffective.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Imidazoles / therapeutic use
  • Indazoles / pharmacology*
  • Indoles / therapeutic use
  • MAP Kinase Signaling System / drug effects*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Oximes / therapeutic use
  • Phosphorylation
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Sulfonamides / therapeutic use
  • Vemurafenib

Substances

  • Imidazoles
  • Indazoles
  • Indoles
  • Oximes
  • Piperazines
  • Protein Kinase Inhibitors
  • SCH772984
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • dabrafenib