Analysis of kinase proteins and their inhibitors bridges information gap between the two major kinase families

Patients with cancer frequently experience therapy resistance. This is often seen when so-called personalized therapy is applied against a kinase protein. In an article, published in November in Trends in Pharmacological Sciences, researchers from the VU, VUMC and University of Copenhagen provide new insights into kinase proteins and their inhibitors. This information can be crucial because therapy resistance is often caused by multiple kinase proteins being active at the same time. Simultaneous targeting those kinase proteins could therefore possibly offer a solution against therapy resistance. In the article, the team of researchers made a comparison between the two main families of kinases: the eukaryotic kinases (such as EGFR and HER2 that frequently drive lung and breast tumors) and the atypical kinases (such as PI3K and MTOR that frequently drive therapy resistance). By comparing the 3D structures of the proteins in both families in detail and enriching them with the location and frequency of mutations and naturally occurring variants (SNPs), the researchers have gained insights into the action of inhibitors against both protein families. This information can be used for more optimal use of existing kinase inhibitors or for the adaptation of existing medicines. The research has been made possible through financial support from Amsterdam Data Science and the Cancer Center Amsterdam Foundation. This work is part of the AI-IMPACT project.

The landscape of atypical and eukaryotic protein kinases. George Kanev, Chris de Graaf, Iwan de Esch, Rob Leurs, Thomas Wurdinger, Bart Westerman and Albert Kooistra, Trends in Pharmacological Sciences, Volume/Issue 40/11, (2019) p. 13.