Exploiting receptor tyrosine kinase co-activation for cancer therapy

Aik-Choon Tan, Simon Vyse, Paul H. Huang
2017 Drug Discovery Today  
Studies over the past decade have shown that Receptor Tyrosine Kinase (RTK) co-activation is prevalent in many cancer types. Compelling data demonstrates that cancers are likely to have evolved RTK co-activation as a generic means for driving tumour growth and providing a buffering system to limit the lethal effects of microenvironmental insults including therapy. In this review, we summarise the general principles of RTK co-activation gleaned from key studies over the last decade. We discuss
more » ... rect and indirect approaches to exploit RTK co-activation for cancer therapy and describe recent developments in computational approaches to predict kinase codependencies by integrating drug screening data and kinase inhibitor selectivity profiles. We offer a perspective on the outstanding questions in the field focusing on the implications of RTK coactivation on tumour heterogeneity and cancer evolution and conclude by surveying emerging computational and experimental approaches that will provide further insights into the biology of RTK co-activation and deliver new developments in effective cancer therapies.
doi:10.1016/j.drudis.2016.07.010 pmid:27452454 pmcid:PMC5346155 fatcat:lv2owxvdofanfc6p2la5wpa4yy