Targeting the MAPK Pathway in KRAS-Driven Tumors

Cancer Cell. 2020 Apr 13;37(4):543-550. doi: 10.1016/j.ccell.2020.03.013.

Abstract

KRAS mutations occur in a quarter of all of human cancers, yet no selective drug has been approved to treat these tumors. Despite the recent development of drugs that block KRASG12C, the majority of KRAS oncoproteins remain undruggable. Here, we review recent efforts to validate individual components of the mitogen-activated protein kinase (MAPK) pathway as targets to treat KRAS-mutant cancers by comparing genetic information derived from experimental mouse models of KRAS-driven lung and pancreatic tumors with the outcome of selective MAPK inhibitors in clinical trials. We also review the potential of RAF1 as a key target to block KRAS-mutant cancers.

Keywords: KRAS-driven cancer; MAPK pathway; clinical trials; lung adenocarcinoma; pancreatic ductal adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Molecular Targeted Therapy*
  • Mutation*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins p21(ras) / genetics*

Substances

  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins p21(ras)