KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment

Cancer Res. 2018 Jan 1;78(1):7-14. doi: 10.1158/0008-5472.CAN-17-2084. Epub 2017 Dec 20.

Abstract

KRAS is one of the most frequently mutated oncogenes in cancer, being a potent initiator of tumorigenesis, a strong inductor of malignancy, and a predictive biomarker of response to therapy. Despite the large investment to understand the effects of KRAS activation in cancer cells, pharmacologic targeting of KRAS or its downstream effectors has not yet been successful at the clinical level. Recent studies are now describing new mechanisms of KRAS-induced tumorigenesis by analyzing its effects on the components of the tumor microenvironment. These studies revealed that the activation of KRAS on cancer cells extends to the surrounding microenvironment, affecting the properties and functions of its constituents. Herein, we discuss the most emergent perspectives on the relationship between KRAS-mutant cancer cells and their microenvironment components. Cancer Res; 78(1); 7-14. ©2017 AACR.

Publication types

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

MeSH terms

  • Extracellular Matrix / genetics
  • Extracellular Matrix / pathology
  • Fibroblasts / pathology
  • Genes, ras / physiology*
  • Humans
  • Mutation
  • Myeloid Cells / pathology
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Signal Transduction
  • Tumor Escape / genetics
  • Tumor Microenvironment / genetics*