Targeting redox balance in mutant p53 cancers

The tumour suppressor p53 is mutated in over half of all cancers and is associated with tumourigenesis, resistance to chemotherapy and poor prognosis. We have recently shown that mutant p53 suppresses glutathione synthesis, disrupting redox balance and providing a weakness that we can exploit using therapies that target anti-oxidant synthesis. This project will determine the mechanism by which mutant p53 suppresses this pathway and develop novel therapeutic strategies in in vitro and in vivo models to target this Achilles heel.

The Clemons Laboratory incorporates fundamental cancer biology research, pre-clinical development of innovative therapeutic strategies and translational research, with a focus on upper gastrointestinal cancers. Our research integrates novel in vitro and in vivo models to investigate functionally important drivers of tumour development and progression, and test new therapies for these cancers.

Upper gastrointestinal cancers are some of the most common causes of cancer related deaths worldwide. Patients frequently present with advanced metastatic disease and resistance to standard chemotherapy is common, leading to poor survival rates for these diseases. Therefore, there is an urgent and unmet need for new therapies for upper GI cancers. Our laboratory has developed pre-clinical models of oesophageal and gastro-oesophageal cancer in order to address important, clinically relevant questions, including how these cancers develop and progress from the very earliest stages through to invasive disease, and how we can therapeutically target different stages of the disease. We work collaboratively with the laboratory headed by Prof. Wayne Phillips in this area of research, and in partnership with clinicians in Cancer Surgery and Medical Oncology to translate our research into the clinic.