Exploiting receptor tyrosine kinase co-activation for cancer therapy

Drug Discov Today. 2017 Jan;22(1):72-84. doi: 10.1016/j.drudis.2016.07.010. Epub 2016 Jul 21.


Studies over the past decade have shown that many cancers have evolved receptor tyrosine kinase (RTK) co-activation as a mechanism to drive tumour progression and limit the lethal effects of therapy. This review summarises the general principles of RTK co-activation and discusses approaches to exploit this phenomenon in cancer therapy and drug discovery. Computational strategies to predict kinase co-dependencies by integrating drug screening data and kinase inhibitor selectivity profiles will also be described. We offer a perspective on the implications of RTK co-activation on tumour heterogeneity and cancer evolution and conclude by surveying emerging computational and experimental approaches that will provide insights into RTK co-activation biology and deliver new developments in effective cancer therapies.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Computational Biology
  • Drug Discovery / methods*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / drug effects*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptor Protein-Tyrosine Kinases