Combining metabolomics and genomics technologies to study platinum-based therapeutic failure in high grade ovarian cancers: from predictive signature(s) to novel therapeutic strategies.

Surgery followed by platinum-based chemotherapy is the standard of care treatment for patients with advanced high-grade serous ovarian cancer. Platinum regimens, however, are characterized by the progressive development of resistance and tumor relapses that ultimately lead to therapeutic failure. Platinum-resistance is a major clinical and socio-economic problem in the treatment of ovarian cancer and the development of new strategies to overcome it is a priority in translational cancer research. Despite the great advances obtained in the field of molecular tumor profiling, the successful integration of such results in the clinical is limited by the lack of preclinical in vivo models with predictive value. Specifically, there is lack of proper biomarkers predictive of response for particular subgroups of patients on platinum-based treatments, and there are not alternative targeted therapies for resistance patients who relapse. The goal of this project is to define, based on a comprehensive and integrated genomic/metabolomic profiling, the crucial determinants of platinum-responsiveness in high-grade serous ovarian cancer.