Mutant p53 as a novel target for cancer
p53 is involved in cell cycle regulation and loss of its function causes uncontrollable proliferation which is observed in cancer cells. Evidence suggests that some of the mutations endow novel biochemical and biological properties to p53 – a phenomenon known as gain of function – and actively contribute to the carcinogenesis process. With this in mind, the multidisciplinary EU-funded ‘Mutant p53 as target for improved cancer treatment’ (MUTP53) consortium aimed to explore the role of mutant p53 in cancer. More specifically, project partners planned to restore p53 tumour suppressor activity by abrogating the gain of function or reactivating the wild type properties of the protein. To achieve this, scientists developed a mouse model with mutant p53, a p53 mutation detection array and small molecules that restore wild type function to mutant p53. Experimental work produced a wealth of information about the biochemical properties of mutant p53, its utility as a clinical marker and ways to target mutant p53 in tumours. Among the project’s other achievements was the identification of small molecules targeting mutant p53. One of them was also tested as a new anti-cancer therapy in patients in a phase I clinical study. The MUTP53 project generated important information on the prognostic and predictive value of p53 mutations in tumours which should be of great value for clinical oncologists in the treatment of cancer patients. Furthermore, it is expected to improve diagnosis and provide major clinical benefit for cancer patients and people in Europe.
