Researchers target ’undruggable’ cancers

A new approach to targeting key cancer-linked proteins, thought to be 'undruggable', has been discovered through an alliance between industry and academia. The study published in Nature shows that two novel and specific small-molecule inhibitors developed by the research teams can bind to and deactivate an enzyme that controls the stability of the p53 tumour suppressor protein. This deactivation allows p53 to be turned on, putting the brakes on cancer growth. The majority of cancers have a faulty or inactive p53 which allows them grow out of control. But despite its important role in cancer, attempts to target p53 directly have hit a number of dead ends. To get around this problem the researchers in this alliance looked at a specialised system, the ubiquitin-proteasome system, which regulates the turnover of a range of proteins, including p53. Focusing on one enzyme in the system, USP7, the researchers were able to show how the two inhibitors exploit a unique binding site in the enzyme.