Dr. Martin Gleave

Dr. Gleave (CM, MD, FRCSC, FACS) is a clinician-scientist and urologic surgeon. His major research focus involves the study of cellular and molecular mechanisms mediating progression of prostate cancer to its lethal stage of androgen independence, and use of this information to develop integrated multimodality therapies that specifically target these mechanisms. Dr Gleave established a role for clusterin as a cancer-related cell survival protein involved in treatment resistance and developed an inhibitor, designated OGX-011, which improved the efficacy of hormone- and chemo-therapies in prostate and other cancer models. He is the scientific founder of OncoGenex Pharmaceuticals Inc. and a Member of the Order of Canada.

Example Project 

“Preclinical Development of a Novel Androgen Receptor Antagonist to Treat Castration-Resistant Prostate Cancer” Prostate cancer (PCa) is one of the leading causes of cancer-related death. In almost all patients, the proliferation and growth of PCa is driven by the androgen receptor (AR). Given this critical role, inhibiting the AR is the standard of care following surgery or radiotherapy. The effectiveness of current therapeutics is usually temporary, with the cancer eventually developing drug resistance. There are no curative treatment options for resistant PCa and these patients have a median life-expectancy of only 20 months. Currently, all clinical anti-AR agents act by direct binding to the AR's hormone binding site. These drugs are therefore vulnerable to mutations which frequently arise at this region. Further, as they are structurally related they cannot be used in combination. There is therefore an unmet need for new therapeutics that inhibit the AR. By combining computer modeling, biological screening and structural biology, we have developed an entirely new class of anti-AR drugs that target a novel region of the AR (called BF3). Our lead compound efficiently inhibits the AR and shows efficacy in both PCa cell lines and xenograft animal models. Building off these proofof-principle studies, this project will progress our lead compound to advanced preclinical development towards clinical trials. We anticipate that these new anti-AR drugs will replace or supplement existing anti-AR therapeutics and will provide new options for treating patients with late-stage PCa.

Research Keywords

Cancer Biology, Treatment Resistance, Prostate Cancer, Androgen Receptor, Molecular Inhibitors