Grant: Project Grant

Targeting DNA repair proteins is a proven strategy for cancer chemotherapy and for personalized medicine approaches. We and others have recognized that the FEN1 protein becomes essential for proliferation in many cancer cell types. Despite this observation, how best to target FEN1 for therapy has remained an open question. Building on our significant preliminary data, we have found a specific region on the FEN1 protein that we believe will provide the greatest therapeutic benefit when targeted. Targeting FEN1 has the potential to both kill tumour cells and stimulate an anti-cancer immune response. In this proposal we address three major questions surrounding the FEN1 target: 1. Which tumour types would benefit from a chemotherapeutic targeting Fen1, 2. How best to target Fen1 for maximum effect in tumours, 3. Which small molecules can elicit the strongest effect on Fen1 in tumour cells with respect to killing and immune stimulation. In this way we will advance a new multifunctional chemotherapeutic with the potential to treat a wide range of tumour types.