Grant: Project Grant

This project aims to develop new strategies to improve the efficacy of treatment options for human ovarian cancer, one of the most lethal malignancies affecting women. Currently, in order to achieve the best treatment, the cancer is removed surgically and the inevitable cancer cells that escape surgery are targeted with therapeutic agents causing DNA damage to tumour cells. Surprisingly, while general non-cancer-specific health risks in response to treatment are well documented (side-effects), very little is known about the cellular biology behind the actual tumour regression. ln other words, the exact response of cancer cells in the tumour reacting to the damage initiated by chemotherapy remains unknown. Damaged cells have many options: they can repair themselves but risk accumulating more DNA damage; they can die; or they can enter a state of permanent growth arrest termed cellular senescence (cellular aging). ln previous research, we unexpectedly found that human ovarian cancer cells strongly undergo therapy-induced senescence, but how this occurs and whether "accelerated cancer aging" influences patient survival remains unknown. Our hypothesis is that therapy-induced cancer senescence during treatment will impact long-term patient survival. Here we propose to extensively characterize ovarian cancer cell senescence at a molecular level (how it works), and to define whether it has a clinical impact on patient survival. This knowledge could help us predict before the start of treatment whether a cancer will respond appropriately, and should help evaluate early, after treatment initiation, whether a cancer is indeed responding. This could also improve our ability to generate new pharmacological targets to manipulate therapy-induced cancer senescence toward beneficial outcomes in ovarian cancer patients