103852A novel small molecule approach to enhance cancer immunotherapyClosedCollaborative R&DInnovate UKA new approach to cancer therapy called 'immuno-therapy' has recently emerged that is now providing unheralded responses in certain cancer types. It is based on the concept that as tumours arise through sequential mutations in their genomes, this also creates 'foreign' antigens that can be recognised and attacked by the immune system. However, tumours also find ways to hide from immune-surveillance and a key advance has been to define, and now reverse, these mechanisms using immuno-therapies. While this is a significant step forward, unfortunately, only a few tumour types, such as melanoma and lung cancer, which possess hyper-mutated genomes (due to high levels of UV or cigarette smoke, respectively) are inherently sensitive to novel drugs that augment immune recognition. Removing the 'cloak of invisibility' is therefore not enough alone in most cancers to be effective. However, if one can find a way to accelerate or boost mutation levels in these non-sensitive cancer types, for example using a second drug that targets a DNA repair mechanism, all cancers could become hyper-responsive to immuno-therapy. To this end, we are developing small-molecule drugs that block a well validated, yet safe to inhibit, DNA repair mechanism. Genetic knock-out studies have shown that inhibiting this specific repair mechanism makes a wide range of cancer types sensitive to immuno-therapies. In this project, we will be optimising these drugs and performing key in vivo tumour response studies to facilitate their rapid progression into further clinical development with a Pharma company.