Grant: Project Grant

Prostate cancer (PCa) is the most common cancer affecting Canadian men and the third cause of cancer-related deaths. PCa is usually first treated by surgery to remove the diseased prostate. However, despite the removal of the tumor, cancer recurrence is frequently observed. The residual cancer cells that metastasize depend on steroid hormones (androgens) for their growth. Androgen deprivation therapy (ADT) is the cornerstone in the management of recurrent, progressive, or metastatic prostate cancer. Recent advances are focussing on more intensive ADT, using the AR-targeting agent enzalutamide (Enza) and the most frequently prescribed androgen synthesis inhibitor abiraterone (Abi) that blocks androgen synthesis in peripheral tissues and tumor cells preventing cancer cells to grow. However, ADT response in CRPC patients varies considerably, and we don't understand the basis of this variability. This knowledge is crucial to optimize treatments in CRPC patients and improve response, as we propose to investigate in this project. We intend to address the prognostic and predictive value of the steroid metabolome in blood, beyond testosterone currently used in clinic to monitor androgen suppression in patients treated by ADT therapy. This is required since numerous other steroids with potent androgenic and biological activities are involved during disease evolution and may play a prognostic role, yet to be addressed. We also intend to measure levels of drugs in the blood of CRPC patients at several time points during treatment. We will then correlate this wealth of important data with the patient's response to therapy to identify important markers of clinical outcomes and drug resistance. The goal of our project is thus to identify biomarkers that could be easily incorporated in clinic. This project will produce information essential to optimize therapy in individual CRPC patient, and ultimately improve survival of men with CRPC.