title: Exploiting receptor tyrosine kinase co-activation for cancer therapy.
abstract: 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.
authors.affiliation: Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: aikchoon.tan@ucdenver.edu.
authors.forename: Aik-Choon
authors.initials: AC
authors.lastname: Tan
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, London SW3 6JB, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Vyse
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, London SW3 6JB, UK. Electronic address: paul.huang@icr.ac.uk.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019295:Computational Biology; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases