Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men of the Westernized world. While early stage disease is frequently curable with surgery or radiotherapy, limited treatment options are currently available for approximately one-third of patients who clinically present with locally advanced or metastatic disease resulting in a poor prognosis for patients with advanced disease. One treatment option that is currently being used for advanced PCa is a medical procedures designed to block androgenic steroids to induce death of prostate cancer since prostate cancer cells typically require these hormones for their growth and integrity. While this treatment is often effective with a response rate of up to 80%, within 1-3 years the tumours inevitably recur as hormone-refractory variants, a condition for which there is no current effective therapy. Thus if we are to have an impact on survival rates of patients with PCa, new therapeutic strategies are required for treating advanced disease. Up to 50% of advanced prostate cancers have acquired mutations in a gene called PTEN that essentially inactivated it. Inactivation of PTEN in prostate cancer is correlated with a poor prognosis. Loss or inactivation of this gene makes prostate cancer cells more resistant to different forms of therapy including chemo-, radiation and hormone-therapy. The development and progression of cancer is dependent on the deregulation of the intricate balance in the rates of cell growth and death. The proposed project addresses how loss of the PTEN gene confers cell with a survival advantage and resistance to therapies. Under ordinary conditions, PTEN keeps growth of normal cells in check by serving as a brake to inhibit cell growth. When PTEN is mutated in cancer, the brakes fail and this confers uncontrolled growth and increased resistance of the cancer cells to chemotherapy and hormone ablation therapy. My lab is actively working on how loss of PTEN protects prostate cancer cells from death signals and we are looking for different ways to block the effects of inactivating PTEN. Results of this study will be directly relevant to development of new therapies aimed at treating the subset of advanced prostate cancers that have lost PTEN.