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A team of scientists and clinicians based primarily at St. Joseph’s Healthcare Hamilton have been awarded a research grant of over $575,000 from the Canadian Institutes of Health Research. The grant will support a three year research project, with the goal of isolating what is believed to be a primary cause of cancer growth in a subset of prostate cancers.

Currently, prostate cancers have an array of treatment options, including surgery, radiation therapy, as well as androgen deprivation therapy (ADT). Androgens are hormones, such as testosterone and dihydrotestosterone, produced in the body by both men and women, but in different amounts so are often referred to as male hormones. Since prostate cancer can be driven by the presence of androgens, ADT is used to reduce the level of androgens in the bloodstream, thereby stunting the cancer growth.

However, prostate cancer may become resistant to ADT, in which case it is called castration-resistant prostate cancer (CRPC). In these instances, tumours continue to grow despite the lack of circulating androgens.

“Something is driving the growth of these tumours, even when we drastically lower the levels of circulating androgens,” said project leader Dr. Damu Tang, a researcher at St. Joe’s in the fields of cell biology and oncology. Dr. Tang is also an Associate Professor of Medicine at McMaster University. His research focuses on breast and prostate cancer, apoptosis, and metabolic diseases.

Dr. Damu Tang (right) in his research lab at St. Joe's. 

Dr. Tang’s project is based on a novel concept – he and his fellow researchers hypothesize that castration-resistant prostate cancer cells produce an enzyme that is normally found in the liver. High levels of this liver enzyme have been detected in the tissues of prostate cancers that progressed to CRPC, suggesting a causal link.

Researchers have previously found evidence that connects the liver enzyme to increased levels of LDL cholesterol. Within prostate tumours, elevated levels of LDL cholesterol can produce androgens, which could explain why CRPC may continue to grow while patients are on androgen deprivation therapy. Essentially, the liver enzyme found within cancer cells produces a steady supply of androgens, allowing continued tumour growth.

“We suspect there may be a local source of androgens being produced inside the tumour, which negate the therapeutic effects of ADT,” noted Dr. Tang.

Disrupting the chain of events that accelerates CRPC growth is one of the main objectives of the research project. To date, Dr. Tang and his team have identified a compound that may hinder the effects of the liver enzyme. Whether this compound will have a beneficial effect towards treating CRPC remains to be demonstrated through pre-clinical in vivo models, and if successful, could lead to a randomized clinical trial.

The Research Institute of St. Joe’s Hamilton has been diligently working to increase its capacity to conduct novel research projects on urologic cancers, including translational research that connects molecular science to clinical practices, all within the walls of our hospital.

“This CIHR grant is just another example of the commitment to the incredible work being done at our new Urologic Cancer Centre for Research and Innovation (UCCRI),” said Dr. Jack Gauldie, Vice President of Research at St. Joseph’s Healthcare Hamilton. “Our vision to connect molecular scientists with clinical urologists and oncologists creates an incredible opportunity for discovery.”

In 2018, the Research Institute of St. Joe’s Hamilton, together with St. Joseph’s Healthcare Foundation, announced a funding commitment for the new UCCRI of $1,000,000 from Mr. John Ribson. In early 2019, a further $250,000 plus up to $750,000 in matching donations – a gift from Mr. Jim Bullock – was announced.

Dr. Anil Kapoor, Director of the UCCRI, hopes the new centre will be able to link discoveries that are being made through groundbreaking lab work, including identification of specific biomarkers and genetic testing, to clinical diagnostics and patient care. Dr. Kapoor and his team hope to gain insight into the risk of reoccurrence, as well as other factors, in determining a suitable treatment for various urologic cancers.

The UCCRI is a part of the Research Institute’s Genitourinary research pillar, created in 2018 to reflect the significant third-party investment and expertise in this area.

Both McMaster University and the University of Guelph are providing resources towards this research project, including animal facilities and testing equipment.

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