Feedback and redundancy in receptor tyrosine kinase signaling: relevance to cancer therapies

Trends Biochem Sci. 2014 Oct;39(10):465-74. doi: 10.1016/j.tibs.2014.08.010. Epub 2014 Sep 16.

Abstract

Mammalian cells have multiple regulatory mechanisms to deal with perturbations in cellular homeostasis, including feedback loops and crosstalk between the major signaling pathways. While these mechanisms are critically required to help cells survive under dynamic physiological circumstances, they also pose an impediment to the effective treatment of cancer. In this review, we describe what has been learned about interactions between receptor tyrosine kinase-dependent signaling pathways, and how this knowledge can be used to design rational and more effective combination therapies for cancer.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Drug Resistance, Neoplasm / genetics
  • Drug Therapy, Combination / methods
  • Feedback
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Oncogenes / drug effects
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • raf Kinases / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • MTOR protein, human
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • raf Kinases