A new study from industry and academia has highlighted a new approach to targeting key cancer-linked proteins that are considered to be ‘undruggable’.
Cancer cell
The study, which involved researchers from the University of Liverpool, has been published in Nature and evaluated a specialised system (the ubiquitin-proteasome system) that regulates the turnover of a range of proteins, including p53 — a faulty or inactive gene that allows cancers to grow out of control.
Focusing on one enzyme in the system, USP7, the researchers were able to develop two small molecule inhibitors and show how they exploit a unique binding site in the enzyme. When applied to cancer cells they lead to a cascade of events that ultimately elevate p53 and promote normal control mechanisms.
Michael Clague, Professor of Cellular and Molecular Physiology, University of Liverpool’s Institute of Translational Medicine, said: “This study provides a proof of principle for a new drug targeting strategy. It opens up opportunities for manipulating proteins relevant to cancer, which have previously been considered out of reach.”
Dr Tim Hammonds, deputy director, Cancer Research UK Cancer Research Technologies, added: “Our alliance model of bringing together the best academics, our own laboratories and leading industry partners means that we can take novel and bold approaches to tackling some of the biggest challenges in cancer.”
“Our study shows that we can target these ‘undruggable’ proteins by specifically targeting the enzymes that control them,” explained Dr Andrew Turnbull, one of the lead researchers at the Cancer Research UK Therapeutic Discovery Laboratories. “Combining this revelation with detailed three-dimensional structures of these enzymes, and their potential targets, means this could be the starting point to develop drugs that target them and the proteins they control.”
The multi-disciplinary research collaboration involving the Universities of Liverpool and Oxford, the Medical Research Council’s Laboratory for Molecular Biology in Cambridge, Cancer Research UK and US based Forma Therapeutics was brought together by Cancer Research UK’s Therapeutic Discovery Laboratories in 2013.