RAS mutations in human cancers: Roles in precision medicine

Semin Cancer Biol. 2019 Dec;59:23-35. doi: 10.1016/j.semcancer.2019.06.007. Epub 2019 Jun 27.

Abstract

Ras proteins play a crucial role as a central component of the cellular networks controlling a variety of signaling pathways that regulate growth, proliferation, survival, differentiation, adhesion, cytoskeletal rearrangements and motility of a cell. Almost, 4 decades passed since Ras research was started and ras genes were originally discovered as retroviral oncogenes. Later on, mutations of the human RAS genes were linked to tumorigenesis. Genetic analyses found that RAS is one of the most deregulated oncogenes in human cancers. In this review, we summarize the pioneering works which allowed the discovery of RAS oncogenes, the finding of frequent mutations of RAS in various human cancers, the role of these mutations in tumorigenesis and mutation-activated signaling networks. We further describe the importance of RAS mutations in personalized or precision medicine particularly in molecular targeted therapy, as well as their use as diagnostic and prognostic markers as therapeutic determinants in human cancers.

Keywords: Cancer; HRAS; KRAS; Mutation; NRAS; Oncogene; Personalized medicine; Precision medicine.

Publication types

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

MeSH terms

  • Alleles
  • Biomarkers, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Frequency
  • Genes, ras*
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease*
  • Humans
  • Molecular Targeted Therapy
  • Mutation*
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • Precision Medicine / methods
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Biomarkers, Tumor