Systematic and comprehensive analysis of mutant p53 proteins in lung cancer in vitro and in vivo

The gene p53 is a well-known tumour suppressor gene that prevents cancer formation. It is the most commonly mutated gene among individuals with a diagnosis of cancer. Through recent advances in DNA sequencing abilities, researchers are now in a position to take a patient’s tumour and identify the exact mutation in p53 and other cancers’ genes, which potentially allows the development of personalized patient care.

This project aims to systematically characterize proteins that bind to mutant p53 in order to identify all the proteins that stabilize and activate mutant p53, as well as the molecular pathways that are co-opted/corrupted by mutant p53. The analysis will occur in living tissues (in vivo) and in a laboratory vessel (in vitro). Once identified, the ultimate goal is to screen for compounds that disrupt these interactions with the hope of finding novel therapeutic strategies to treat patients harbouring these specific p53 mutations. The project findings will possibly extend to other cancers associated with p53 mutations.

The project is being implemented by the Lunenfeld-Tanenbaum Research Institute at Mount Sinai
Hospital (Toronto), the Weizmann Institute of Science (Israel), the Universidade Federal do Rio Grande do Sul (Brazil), and the Universidad San Martin (Argentina).

This project was selected for funding through the third research competition of the Joint Canada-Israel Health Research Program, a partnership between IDRC, the Canadian Institutes of Health Research, the Israel Science Foundation, and the Azrieli Foundation.