Defining the role of mutant p53 in the response of cancer cells to microenvironmental stress

In a growing tumor, cancer cells are chronically exposed to stress from the altered tissue environment, high mutational rate, and chemotherapy. Cancer cells can adapt and survive in these conditions; moreover, the  activation of molecular pathways of response to stress can actually promote malignant progression. Within a project aimed at understanding the genetic determinants that enable adaptation of cancer cells to stress, the Fellow will study the impact of two different tumor suppressor genes, TP53 and DAB2IP, whose loss-of-function is known to promote aggressiveness in multiple types of tumors. This project aims to improve our knowledge of the mechanisms that allow tumor cells to adapt and survive under chronic stress, and in particular on the role played by specific TP53 mutations. Such knowledge will aid the development of targeted therapies, and provide new parameters for choosing more effective individualized treatments.