Exploiting synthetic lethality for cancer treatment: improving the activity and specificity of novel MRE11 inhibitors

Traditionally, the choice of cancer treatment was based on the organ where the cancer originated. However, molecular understanding of cancer has allowed development of targeted treatments, where drug choice is tailored to specific genetic changes in cancer cells. This promising approach is called personalised treatment and is widely considered to be the future of cancer therapy.

Research has identified genetic changes associated with cancer development in numerous genes – many of these changes can cause weaknesses in the cancer cells that can be targeted by novel drugs.

We have previously identified a potential treatment target, the protein MRE11. Cancer cells often depend on MRE11 overexpression for survival and proliferation. We have therefore initiated the development of novel MRE11 inhibitors. So far, we have identified 18 novel and distinct compounds which can inhibit MRE11. Our preliminary data and published results suggest that these inhibitors have the potential to treat a range of cancers.

The aim of this project is to develop better MRE11 inhibitors and test these for a range of cancer types. The long term aim of our research is to advance one or more of our novel inhibitors towards clinical application, using them to target various cancers that depend on MRE11.