KRAS Alleles: The Devil Is in the Detail

Trends Cancer. 2017 Oct;3(10):686-697. doi: 10.1016/j.trecan.2017.08.006. Epub 2017 Sep 12.


KRAS is the most frequently mutated oncogene in cancer and KRAS mutation is commonly associated with poor prognosis and resistance to therapy. Since the KRAS oncoprotein is, as yet, not directly druggable, efforts to target KRAS mutant cancers focus on identifying vulnerabilities in downstream signaling pathways or in stress response pathways that are permissive for strong oncogenic signaling. One aspect of KRAS biology that is not well appreciated is the potential biological differences between the many distinct KRAS activating mutations. This review draws upon insights from both clinical and experimental studies to explore similarities and differences among KRAS alleles. Historical and emerging evidence supports the notion that the specific biology related to each allele might be exploitable for allele-specific therapy.

Keywords: KRAS; RAS; alleles; cancer genetics; oncogene.

Publication types

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

MeSH terms

  • Alleles*
  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Molecular Targeted Therapy
  • Mutation*
  • Neoplasms / epidemiology
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors
  • Proto-Oncogene Proteins p21(ras) / chemistry
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Structure-Activity Relationship


  • KRAS protein, human
  • GTP Phosphohydrolases
  • Proto-Oncogene Proteins p21(ras)