Researchers uncover new approach for targeting p53

An alliance between industry and academia created by Cancer Research UK has discovered a new approach to targeting key cancer-linked proteins previously deemed ‘undruggable’.

The multidisciplinary research collaboration - brought together by Cancer Research UK’s Therapeutic Discovery Laboratories and including scientists at FORMA Therapeutics, the Universities of Oxford and Liverpool, and the MRC Laboratory for Molecular Biology in Cambridge - has developed two novel and specific small-molecule inhibitors shown in a study to bind to and deactivate an enzyme that controls the stability of the p53 tumour suppressor protein.

The majority of cancers have a faulty or inactive p53 which allows them to grow out of control, but previous attempts to target the protein have failed. Deactivation of the enzyme controlling its stability allows p53 to be turned on, thereby stalling cancer growth.

"Our study shows that we can target these ‘undruggable’ proteins by specifically targeting the enzymes that control them," said 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."