Rising Star Recipients

Prostate Cancer Canada and Movember are proud to announce the recipients of the inaugural Rising Star in Prostate Cancer Research awards. These investigators represent the next generation of leading prostate cancer researchers across Canada.

Principal Investigator: Xuesen Dong
Host Institution: Vancouver Prostate Centre
Title: Androgen receptor signaling in castration 
resistant prostate cancer
Principal Investigator: Anthony Joshua
Host Institution: Princess Margaret Hospital
Title: Exploiting autophagy for therapeutic gain in prostate cancer
Principal Investigator: Hon Leong
Host Institution: London Health Sciences Centre
Title: Prostate cancer microparticles in plasma as a fluid biopsy for screening of prostate cancer
Principal Investigator: Éric Lévesque
Host Institution: Université Laval
Title: Novel prognostic markers of prostate cancer

Principal Investigator: Xuesen Dong
Host Institution: Vancouver Prostate Centre
Title: Androgen receptor signaling in castration resistant prostate cancer

Androgens are steroid hormones produced and secreted by the testes, which have been strongly implicated in prostate cancer. These hormones act by activating a protein inside the cell called the androgen receptor (AR). AR regulates several genes to promote tumor growth. Therefore, the primary treatment for advanced prostate cancers is the androgen depletion therapy, which either blocks androgen synthesis or prevents androgens from activating AR. 

However, the effectiveness of this therapy is temporary. Many cancers progress into the androgen insensitive stage (also referred to as castration-resistant prostate cancer, CRPC), for which no curative option is available. One of the possibilities for the development of CRPC is that prostate cancer cells generate shorter forms of AR, called AR variant (ARv). ARv is constitutively active even under androgen free environments, and has been shown to promote prostate tumor growth regardless androgen deprivation therapy.

The aim of our research is to advance our understanding by studying how ARv is generated, which is information that will be important to develop therapeutic means to prevent Arv from synthesis in CRPC patients. We believe our efforts will benefit prostate cancer patients in Canada.

Dr. Dong conducted his post-doctoral training in prostate cancer research at Mount Sinai Hospital under the supervision of Dr. Stephen J. Lye and at Vancouver Prostate Centre under the supervision of Dr. Paul Rennie. He has been with the Vancouver Prostate Centre since 2007 and is an Assistant Professor at the University of British Columbia.

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Principal Investigator: Anthony Joshua
Host Institution: Princess Margaret Hospital
Title: Exploiting autophagy for therapeutic gain in prostate cancer

Currently, with 26500 new cases of prostate cancer diagnosed yearly and 4000 deaths per year in Canada, novel treatments and approaches for prostate cancer are sorely needed. In the current proposal, we aim to take advantage of recent insights into prostate cancer tumour biology based on our previous work to propose both a novel paradigm for a treatment adjunct across a broad range of prostate cancer treatments such as radiation, hormonal therapies and chemotherapies.

Cancer cells are often under stress in the cancer microenvironment, commonly lacking oxygen, sugar as well as other essential nutrients. When this occurs, the cancer cells may turn to a newly discovered strategy known as autophagy to survive. This process involves recycling parts of the cell that are no longer needed to be used as fuel for survival. We have recently refined the use of a non-toxic autophagy inhibitor, which is actually the commonly used anti-acid medication pantoprazole, in high doses.

In addition, we have data suggesting that this approach will be even more potent in stressing and therefore killing the cancer cells if we treat the cells with metformin, a commonly used diabetic medication that we have recently proved to fool the cancer cell into thinking it is starving but inhibiting a protein known as mTOR. By using these two treatments together, we hope to improve the efficacy of radiation, hormonal and chemotherapy for prostate cancer. To supplement this work, we will look at the importance of autophagy in a clinical trial we are running with pantoprazole to see if we can predict outcomes by examining prostate tissue. Finally, using the unique facilities in our laboratory, we will carry out a “screen” for new ways to target and kill prostate cancer by reducing 78000 different genes in the prostate cancer and seeing what effect they have on the survival ability of the cells.

This research is aligned with the goals of Prostate Cancer Canada by proposing a novel treatment paradigm for men that will rapidly be adaptable to the clinic across a number of treatment modalities in prostate cancer care to improve outcomes.

Dr. Joshua completed his Fellowship Program in Medical Oncology at Princess Margaret Hospital and the University of Toronto under the supervision of Dr. Ian Tannock. He has been an active staff member at Princess Margaret Hospital and an Assistant Professor with the University of Toronto since 2008.

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Principal Investigator: Hon Leong
Host Institution: London Health Sciences Centre 
Title: Prostate cancer microparticles in plasma as a fluid biopsy for screening of prostate cancer 

I propose translational prostate cancer research to assess the clinical usefulness of a blood test that I hypothesize will be superior to the PSA test because it will distinguish patients with benign prostatic hyperplasia (BPH) from patients with prostate cancer (PCa). The blood test measures prostate cancer fragments in the blood as opposed to quantitating PSA levels which are high in both BPH and PCa patients. This proposal addresses a major research goal for PCC, because this blood test will prevent a large majority of men from being submitted to unnecessary prostate biopsy, which has various side effects associated with rectal bleeding and urinary tract infection. 

Currently, 75% of men with high PSA levels do not have PCa according to their biopsy, and decreasing this by every 5% would eliminate ~165,000 unnecessary biopsies and 6,930 hospitalizations each year in North America. Currently, prostate cancer fragments, also known as microparticles, are an emerging topic in oncology research, but many researchers lack the instrumentation needed to translate this work into the clinic. The focus of this work is to validate the clinical utility of our prostate cancer microparticle test as a screening tool and to compare its accuracy to serum PSA levels.

We will use a specialized instrument that analyzes cell fragments in a high-throughput, multi-parametric manner called the nanoscale flow cytometer. This instrument will enumerate microparticles that bind prostate-specific and cancer specific markers present in minute quantities of blood. We will conduct a prospective study in which we will analyze PSA levels and PCa microparticles in the blood of consenting patients prior to biopsy of their prostate. Pending the histological assessment of their prostate biopsy, which is the primary means of PCa diagnosis, we will compare the accuracy of PSA and our prostate cancer microparticle test with the help of statisticians and clinicians. In this large prospective trial, we anticipate that this blood test will be more accurate than PSA and generate tremendous cost savings and health benefits to all potential prostate cancer patients.

Dr. Leong is an Adjunct Professor with the Department of Oncology at the University of Western Ontario (London) and a Scientist with the Lawson Health Research Institute. He completed his post-doctoral fellowship at the London Regional Cancer Program under the supervision of Dr. Ann Chambers

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Principal Investigator: Éric Lévesque
Host Institution: Université Laval
Title: Novel prognostic markers of prostate cancer 

One out of six men will be diagnosed with PCa during his lifetime. Although there has been a decline in mortality rate due to early detection and better therapies, our ability to predict the progression and metastatic behavior of a patient’s cancer is still very limited. Risk of disease progression differs greatly between individuals, and the variability in clinical outcome further emphasizes the need to find and characterize novel markers of progression. 

Current prognostic tools that include clinico-pathological parameters lack sufficient accuracy to effectively predict recurrence. Our primary goal is thus to discover genetic markers in steroid-regulating pathways associated with progression independent of current prognostic factors and to characterize at the molecular level these novel markers of progression. We thus propose to conduct classical genomic approaches to uncover and validate such eagerly awaited markers in well-established cohorts. We will also characterize, at the molecular level, how these SNPs influence hormone exposure and action that lead to cancer progression using complementary approaches. 

Our viewpoint is that host genetic factors could be incorporated into cancer management in a number of ways, including:
i)    the individualized clinical use of existing agents, according to host factors and 
ii)    future development of therapeutic agents that target adverse effects of host factors.

The prediction of risk of progression is clearly important for personalized treatments and follow-up strategies. It is thus crucial to identify patients with aggressive disease most susceptible to relapse and to understand the underlying genetic mechanisms involved in progression to adapt treatment strategies targeting defective molecular pathways. Development of methods to identify indolent PCa, who can safely forego treatment, also represents a major contemporary challenge. Our ultimate goal is thus to develop molecular tools to guide therapeutic decisions and design novel therapeutic interventions to prevent progression based on inherited genetic variations.

Dr. Lévesque completed his post-doctoral fellowship under the supervision of Dr. Chantal Guillemette in the Faculty of Pharmacy at Université Laval. He is currently an Hematologist-Oncologist and Assistant professor, Faculty of Medicine, Université Laval and CHU de Québec.

PCC would like to recognize the Movember Foundation as an important funder of this program.

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