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Alexander Wyatt, PhD
Vancouver Prostate Centre

Mentor: Colin Collins, PhD

Proposal Title: A Next-Generation Model to Neuroendocrine Prostate Cancer

  • Neuroendocrine prostate cancer is a very aggressive, lethal subset of advanced prostate cancer that is poorly understood, partly due to the lack of a good animal model to study the disease in.
  • Dr. Wyatt has developed a next-generation mouse model to study NEPC by transplanting patient tumor tissue into mice.
  • Dr. Wyatt will conduct high coverage, deep sequencing of DNA and RNA from the patients’ primary tumors and the mouse model to reveal mechanisms and markers underlying the development of lethal NEPC. These studies will then be clinically validated in large patient cohorts, experimentally functionalized and therapeutically targeted.

What this means to patients: Dr. Wyatt’s studies will improve our understanding of advanced, lethal neuroendocrine prostate cancer; aid risk stratification; and identify candidate therapeutic strategies to help prevent, or improve the treatment of, NEPC.

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Barbara Lelj Garolla, PhD
Vancouver Prostate Centre

Mentor: Martin Gleave, MD

Proposal Title: Characterization of the molecular chaperone Clusterin, a key player in treatment-resistant prostate cancer, to facilitate discovery of small molecule inhibitors

  • Clusterin (CLU) is a protein highly overexpressed in castration-resistant prostate cancer (CRPC) that confers treatment resistance upon cancer cells and is correlated with poor prognosis.
  • Dr. DiBard proposes to study the biochemical and biophysical properties of CLU, detailing its interactions with other proteins in the cancer cell.
  • She will also identify the precise three-dimensional structure of the clusterin protein. The results of these structural studies will guide the design, screening and testing of inhibitory molecules against CLU.

What this means to patients: Elucidation of the precise 3-D structure of the pro-cancer protein, Clusterin and the identification of potent Clusterin-inhibitors will facilitate the discovery of novel drugs and effective therapies for CRPC patients.

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Anthony Michael Joshua, MBBS, PhD
Princess Margaret Hospital

Mentor: Neil Fleshner, MD

Proposal Title: A Randomized Pilot Study of the effect of Metformin in patients undergoing Active Surveillance for Prostate Cancer

  • The medication metformin is currently approved for diabetes and polycystic ovarian syndrome. Dr. Joshua proposes an interventional study to evaluate the use of metformin in preventing/delaying prostate cancer progression among men with low-risk disease.
  • Dr. Joshua proposes that the insulin-lowering activity of metformin will be effective against prostate cancer as insulin has pro-survival effects on tumors. Further, obesity/ high insulin levels are known adverse prognostic factors for prostate cancer.
  • In the interventional study, Dr. Joshua will study the effects of metformin on prostate tumor cell signaling and proliferation. He and his team will also quantify the tolerability of different doses of metformin in these low-risk prostate cancer patients, evaluating their effects in delaying cancer progression.

What this means to patients: These studies will define a subset of low-risk prostate cancer patients who will benefit from therapy with the medication, metformin in the active surveillance setting. These results will help in the design of a larger definitive trial focused on subgroups defined through this proposal.

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Shyh-Dar Li, PhD
Ontario Institute for Cancer Research

Mentor: Ian Tannock, D, PhD

Proposal Title: Enhance therapy of metastatic castration-resistant prostate cancer by improving docetaxel delivery.

  • Chemotherapy with docetaxel is the treatment of choice for prostate cancer patients with progressive disease. However, most patients go off docetaxel due to poor drug tolerability, limited efficacy, and the development of drug resistance.
  • Dr. Li and his team have developed a nanoparticle formulation for docetaxel (named Cellax) that exhibits increased tumor delivery, reduced toxicity and enhanced efficacy in multiple preclinical models.
  • In this study, Dr. Li will compare the efficacy of Cellax with docetaxel in terms of multidose toxicity, treatment of metastatic treatment-resistant disease and efficacy in docetaxel-resistant cancers.

What this means to patients: The Cellax nanoparticle formulation for docetaxel delivery to metastatic tumors holds promise and this study will evaluate the efficacy of this formulation in bone metastatic models of disease and under the docetaxel-resistant tumor setting.