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Martin Gleave, M.D., FRCSC, FACS

Professor, Department of Surgery, University of British Columbia
Director, Clinical Research, The Prostate Centre, Vancouver General Hospital
Director of Basic Science Research, Division of Urology
Active Staff, Division of Urology, Vancouver General Hospital
Research Scientist, Department of Cancer Endocrinology, BCCA
Consultant Urologist, Department of Urology, University of Washington

Jack Bell Research Centre
2660 Oak St.
Vancouver, BC
Canada V6H 3Z6
Office: 604 875-4818
Fax: 604 875-5654
E-mail: gleave@interchange.ubc.ca


Research Interest

The 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. To facilitate study of these complex multifactorial processes, we use several tumour models that progress from an androgen-dependent to -independent state after androgen withdrawal. Collectively, these model systems mimick the human disease by undergoing apoptotic tumour regression after castration with rising serum PSA levels and tumor growth during progression to androgen independence. Genes that are differentially expressed during progression to androgen independence are being characterized using comparative hybridization of cDNA microarrays. Information and technologies gained from the unraveling of molecular mechanisms mediating androgen resistance are being tested for functional relevance and pre-clinical development. For example, preclinical studies and Phase II human studies confirmed the feasibility of intermittent androgen suppression (IAS) in patients with prostate cancer, and led to initiation of Phase II and Phase III trials across Canada (NCIC), the USA (SWOG), and in Europe. Ongoing experiments are targeting the molecular basis of androgen independence and chemoresistance. Antisense Bcl-2 oligonucleotides enhances chemosensitivity, castration-induced apoptosis and delayed time to androgen independence, providing preclinical evidence to support a Phase I/II study of antisense Bcl-2 oligos with mitoxanthrone in patients with advanced prostate cancer at our institution. More recent studies have established the role of TRPM-2 as an apoptosis related cell survival gene implicated in the development of androgen independence and chemoresistance. Antisense TRPM-2 oligonucleotides significantly reduced TRPM-2 levels and improved efficacy of androgen withdrawal therapy and cytotoxic chemotherapy. This data provides compelling justification for pursuing clinical studies.




Davison BJ, Goldenberg SL, Gleave ME, Degner LF. Provision of individualized information to men and their partners to facilitate treatment decision making in prostate cancer. Oncol Nurs Forum. 30 (1) : 107 - 14. 2003


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