Mutant p53 as a target for improved cancer treatment

This project is a multi-disciplinary approach to explore and exploit the contribution of mutp53 to cancer. We will investigate in depth the molecular properties of mutp53: structural studies will pinpoint the changes that particular mutations inflict on t he structure of p53, and allow the classification of mutp53 into distinct subclasses. Biochemical studies will explore the mode of action of mutp53 within cells, including its impact on patterns of gene expression, identification of specific DNA sequences targeted by mutp53, and discovery of mutp53-interacting cellular proteins. Preclinical models for mutp53-driven cancer will be developed.. We will aim at translating this information into better cancer therapy by addressing the clinical relevance of part icular p53 mutations in human cancer, and particularly its impact on the patient’s response to chemotherapy. We will also explore novel therapies targeted at mutp53 and mutp53-expressing tumor cells. The scope of this project covers b asic molecular biology to Phase I clinical trial. Owing to the extremely high frequency of p53 mutations, success of this project will impact on a very large number of cancer patients worldwide.