Cancer is among the leading causes of morbidity and mortality worldwide. The efficacy of the available anticancer chemotherapy remains quite limited, and generally associated with increasing drug resistance and severe side effects. The discovery of new anticancer agents is therefore a major medical priority. The p53, p63 and p73 tumor suppressors are key therapeutic targets in cancer. Inactivation of these p53 family proteins by interaction with MDM2 and MDMX, and mutation of p53 are common events in human tumors, leading to two major anticancer therapeutic strategies: inhibition of the MDMs interaction with p53 family proteins, and mutant (mut) p53 reactivation. (…) Collectively, relevant advances in anticancer therapy are expected to emerge from this project. A widely multidisciplinary and collaborative research team from recognized national and international research centres, and with a robust expertise in the field of this proposal, will strongly support the project toward the achievement of the proposed goals.