Cancer therapies such as chemotherapy and radiotherapy aim to kill cancer cells by causing damage to their DNA. However, cancer cells often resist treatment because they have mechanisms in place that allow them to repair their DNA. Understanding how this DNA repair takes place is essential to develop more effective cancer treatments.
Associate Professor Peter McHugh, a group leader at the MRC WIMM and the Department of Oncology, has been awarded a collaborative award by Cancer Research UK to investigate this problem. The project, to be developed in collaboration with Prof Chris Schofield (Department of Chemistry) and Prof Opher Gileadi (Nuffield Department of Medicine) will focus on human metallo-β-lactamase (MBL)-fold nucleases, important players in a cell’s DNA repair machinery. Using a combination of cell biology, genetics, structural biology and chemical biology, they hope to understand in detail how this machinery repairs DNA in a healthy context, and how it is exploited by cancer cells. These results will be used to develop a screen for potential drugs that can inhibit the activity of MBL-fold nucleases. These inhibitors could have antitumour properties or help make existing cancer therapies more efficient, as cancer cells would no longer be able to repair their DNA.
“By defining the mechanism of action of MBL-fold nucleases and identifying strategies for their inhibition, we will enable efforts to exploit this druggable target” said Assoc Prof McHugh. New drugs targeting MBL-fold nucleases could, in the future, be combined with existing therapies to increase their efficiency and reduce side-effects.