Overcoming drug resistance and improving cure rates

Lead researcher - The late Professor Tessa Holyoake and Dr David Vetrie, University of Glasgow
Targeting p53, c-Myc and PRC2 regulatory hubs: A systematic and stratified approach to deliver new therapeutics for CML
Amount awarded: £1,755,446
Award start date: 08 Jun 2015
Award duration: 5 years

The treatment for patients with chronic myeloid leukaemia (CML) has improved greatly over recent years following the introduction of new drugs called kinase inhibitors, specifically designed to block the activity of the protein which drives the leukaemia – BCR-ABL1. However there are subgroups of patients with CML who respond poorly to kinase inhibitors or develop drug resistance over time. We wish to find predictors of which patients will do well with these drugs and which require alternative approaches.  In addition, because the leukaemia stem cells that maintain the leukaemia in the bone marrow are not killed by kinase inhibitors, very few patients can currently be cured and most have to stay on treatment for the rest of their lives and suffer significant side effects. Our programme of work has uncovered three new networks of proteins in leukaemia stem cells that work together to aid cancer cell survival. Over the next 5 years we wish to investigate how these proteins interact with each other and how they may be targeted with new drugs to improve the outcome for patients with CML. Overall we wish to significantly improve CML cure rate and provide new forms of treatment for patients with drug resistance and advanced phase disease.