Ricerc@Sapienza

Cancer is the second cause of death worldwide, constituting a crucial medical and socio-economic challenge. Gene/environment interactions play a pivotal role in the development of cancer. Environmental pollutants, several of which act as endocrine disruptors (EDs) may interact with genetic background to increase the risk and modulate aggressiveness of many different cancers, including endocrine-related breast (BC) cancer.
This project aims at dissecting the complex interplay between BC genomic landscape and exposure to EDs by:
1. Defining the molecular mechanisms of action of selected EDs in genetically defined preclinical models of BC in vitro (WP1);
2. Understanding the role of EDs in tumor development and progression in vivo employing different mouse models of BC (WP2);
The overall aim of the project is to identify driver mechanisms/molecular mediators through which EDs exert their tumor-promoting activity; potentially actionable genetic alterations/signaling pathways could be then exploited to develop targeted prevention/treatment strategies aimed at reversing such tumor-promoting effects. The proposed experimental strategies aim at validating potential candidates identified by literature and our preliminary data on one hand, and discovery-based identification of new potential candidates, using integrated approaches in preclinical models in vitro and in vivo. Finally, in vitro and in vivo models will recapitulate the entire process from pre-neoplastic changes to overt tumor progression, potentially allowing for translation of the results achieved in a preventive setting.
Altogether, this project will propose several innovations, by linking external sources of exposure to biomarkers, disease phenotypes, and potential molecular targets, which could be widely exploited in diagnostic, therapeutic, preventive and health-economic applications.