How We Help

Up to 10% of all prostate and breast cancers are thought to be caused by alterations (mutations) in cancer-related genes that are inherited and passed on from generation to generation. There are genes that, when mutated, increase the risk for breast cancer in women and prostate cancer in men. Unfortunately, men with a personal and family history of prostate cancer are often not offered genetic testing of prostate cancer-related genes. As a result, many men (and family members of those men) that have a prostate cancer-related gene mutation are not aware of it. This is a stark contrast to families with a history of breast, ovarian or colon cancer where genetic testing for cancer-related genes is readily offered. If men are identified to have an inherited prostate cancer-related gene mutation they may be eligible for more advanced screening, preventative strategies and personalized treatment of their disease. What’s more, identifying inherited gene mutations allows other family members to undergo genetic testing to see whether they are at increased risk for cancer as well.

Prostate cancer is responsible for more than 10% of all cancer related deaths in men, yet a significant portion of men diagnosed with prostate cancer will not die from the disease. Therapy often consists of surgery and/or radiation to remove or destroy the prostate, which results in significant side effects that include urinary incontinence and erectile dysfunction. There is an urgent need for a simple non-invasive test that can accurately identify those patients in need of aggressive treatment while sparing many from unnecessary treatment. This research proposal has two main goals; 1) to validate a blood-based diagnostic test to diagnose prostate cancer, and 2) to validate a pathology test to predict the progression of prostate cancer to metastasis. These tests will build upon exciting recent research in our group, where we found two novel biomarkers that can accurately predict which patients have prostate cancer, and whether these patients will eventually develop metastasis. In this project, we will validate the diagnostic potential of our ghrelin and CD151 tests in large cohorts of prostate cancer patients to determine whether to move them to routine use in the clinic. Our initial data indicates that both of these tests will do a better job of predicting outcomes, allowing for a more confident risk assessment of prostate cancer at diagnosis, during active surveillance, and during treatment.

Prostate cancer is often incurable and current therapies have marginal effects that fail to eliminate the disease. Drs. Shayegan and Austin, and Ph.D. candidates Al-Hashimi and Hoogenes will combine basic science and translational research to investigate novel treatments to reduce prostate cancer cell growth and metastasis. This project will examine blood samples from prostate cancer patients and the use of mice to determine if disrupting the binding of anti-GRP78 autoantibodies to the cell surface of GRP78, a protein, through the use of a drug used to reduce blood clots in prostate cancer patients, could also serve as a treatment for reducing metastatic prostate cancer growth. This could prove to be a simple and novel treatment for prostate cancer through the use of a drug, heparin, which can be easily implemented.

The purpose of this research project is to look at rectal toxicity using the most modern imaging systems available for planning and that directly mounted on the linear accelerators we use to treat our patients. Previous attempts to assess daily rectal movement and its impact on toxicity were hampered by the relatively poor quality of the onboard images when compared to diagnostic scans. Recent advances in both onboard imaging hardware and treatment complexity make it possible to re-examine rectal toxicity including the daily variations in movement and filling. This study could change the way we modulate and direct the beams of radiation in our plans as well as the way we align our patients for treatment.

This study will evaluate the patient satisfaction in regards to a nurse and pharmacist led clinic that will include a call back program, which will utilize videoconferencing to evaluate and support metastatic prostate cancer patients treated with oral anti-cancer drugs. Through this study we also aim to examine the feasibility of use of the telemedicine equipment as well as analyze any interventions made for the resolution of side effects reported by the patients during the teleconference with the nurse and pharmacist team.

Bitter taste is detected by receptors called Tas2Rs, and it is thought that since the majority of poisons that plants produce are bitter in taste, the ability to sense bitter taste helped animals to avoid harm. Bitter taste receptors are not only expressed in the mouth, but have also been found outside of the mouth and have recently been found on the surface of cancer cells, and are far less abundant in cancer cells compared to normal cells. Our main question is why are these proteins expressed on cancer cells? Often drugs used during chemotherapy are bitter in taste; is it possible that cells expressing fewer receptors present could explain why some chemotherapy drugs don’t work? If we better understand why bitter taste receptors are found on cancer cells and how we can control their expression we could potentially find new ways to kill cancer cells. These new drugs could be used with currently used chemotherapy and help to reduce cancer reoccurrence.

Radiation therapy plays an important role in the management of prostate cancer. Higher radiation dose is proven to be better in terms of disease control. Brachytherapy is an excellent way to increase the dose to the prostate, however is limited by short-and long-term bowel and urinary side effects. An alternative to increasing the dose to the whole prostate would be to define a dominant area that would benefit from dose escalation. The advances done in radiology, especially with the MRI allows us to identify areas of higher-grade tumour. We propose to combine informations from the MRI with our HDR brachytherapy monotherapy program in a study of MRI Assisted Focal Boost Integrated with HDR Monotherapy Study in Low and Intermediate Risk Prostate Cancer Patients (MARS).

Prostate cancer that has spread to other body parts is typically treated with hormonal therapies or chemotherapy. However, for a sizeable subgroup of patients with limited spread (maximally 5 sites) a novel form of radiation therapy called stereotactic ablative radiotherapy (SABR) is increasingly used. SABR enables the administration of very precise and high radiation doses, which can eradicate tumors in various body sites and with limited side effects. Following SABR, some patients may remain tumor-free for prolonged periods of time, whereas others may rapidly develop extensive tumor spread at other sites. There are no tests to predict these two distinct behaviors to date. Hence, Dr. Emmenegger and his research team aim to study genetic material from tumor cells that is detectable in the bloodstream in order to find markers predicting patients most likely to benefit from SABR. The genetic information gained may also be useful to choose additional cancer therapies that could be combined with SABR to further improve outcome.

Our laboratory works to find gene-based tests to distinguish between men whose prostate cancer can be safely monitored and those with harmful cancers who would benefit from a definitive treatment. As prostate cancer harms patients by spreading outside the prostate to distant organs (a process called metastasis), this proposal will study a gene called “ezrin,” which may be a master regulator of metastasis. In particular, we will study whether measuring ezrin levels distinguishes harmless from harmful cancers, and whether blocking ezrin might slow or prevent the spread of prostate cancer.

The human gut is home to over 100-trillion bacteria, a number that is so large that it means that humans carry more bacterial cells in their bodies than human cells. These bacteria in our gut play a central role in breaking down and extracting nutrients from the food we eat. These nutrients determine the health of the host and how the host responds to environmental stresses. The GI microbiota contributes substantially to overall health and several recent studies have alluded to differences in diet that may alter the risk of developing prostate cancer, although these studies have not been consistent. Here we propose a unique method that involves analyzing each bacterial cell individually and then identifying the bacteria to better understand what changes are seen in the GI microbiota of men with prostate cancer. These indepth studies will serve to provide substantial information on the role the GI microbiota plays in the development of prostate cancer and may lead to the development of probiotic therapies and more accurate screening tests for prostate cancer.

The needle core biopsy of the prostate is the gold standard technique for confirming if there is cancer and how aggressive the cancer is. However, it is also the weakest link in the management of prostate cancer patients because it carries a 15-20% sampling error rate because the high risk tumors may be missed by the needles used during the biopsy procedure.  This means that 15-20% of patients are getting inaccurate information regarding their tumor and for some men, the prostate is removed when it should not have been, or it is not removed immediately when it should be.  We have developed a “liquid biopsy”, which is a non-invasive alternative to the needle biopsy of the prostate, with our preliminary data exhibiting a 89% accuracy rate.  We propose to apply this novel blood test/”liquid biopsy” on men who have provided blood before their biopsy, who have gone onto have their prostate removed because the needle biopsy suggested the presence of intermediate-/high-risk prostate cancer.  Our “liquid biopsy” only requires a teardrop of blood, consumes minimal reagents, and takes only 5-6 minutes to analyze.  We will analyze almost 200 blood samples belonging to men who have had a biopsy and subsequent prostatectomy and determine how accurate our “liquid biopsy” is to the final pathology report which will provide the true readout of the prostate cancer.  This will also be compared to the needle core biopsy result, and we anticipate our “liquid biopsy” to be more accurate than the needle core biopsy.  The impact of this improvement is significant, it will help surgeons determine which patients should get surgery immediately and which patients should defer surgery until the tumor becomes a “high-risk” cancer, which could also be detected with this same “liquid biopsy” blood test.

During the past three years, we have studied intermediate risk prostate cancer patients. We have collected blood samples and isolated circulating tumor cells (CTCs). We have characterized the 3D telomeric profiles of CTCs. We were able to stratify the patients into those with stable, transitional and progressive disease. In the proposed study, we will specifically focus on patients who have 3D telomeric profiles indicative of disease progression. We will find out what specific genetic changes (mutations) these CTCs carry. This will allow for targeted treatments, i.e. treatments that are truly personalized for each individual patient.

It is often difficult to see if prostate cancer has spread beyond the prostate gland using standard tests. Fortunately, there is a new imaging test that could help.  This test uses a medicine, called a tracer, that binds to prostate cancer cells.  It is attached to an emitter that can be detected by PET imaging.  This tracer is available for research in Ontario and across the United States and Europe, but is very expensive.  We hope to make the tracer here in Montreal in a research laboratory in order to support trials for patients in Quebec in a way that is more affordable.  By having access to this PET imaging tracer, we hope to prove that it is a better way to detect prostate cancer outside the prostate gland.  This will help patients in Quebec make better decisions about their treatments and have access to better imaging tests.

More prostate cancers are now detected at an early stage, largely due to the PSA test. While some cancers are slow‐growing and unlikely to threaten a man’s life, others are aggressive and require immediate treatment. Unfortunately, we currently lack reliable tools to tell us which course a tumour will take, resulting in unnecessary ‘over‐treatment’ of men with non‐threatening cancer, and missed or delayed treatment of aggressive disease. An exciting recent discovery is that cancer cells release small packages of information, called extracellular vesicles (EVs), into body fluids such as urine. EVs contain an enriched source of ‘red flags’ for disease, called biomarkers. We aim to isolate EVs from patient urines, using a rapid and efficient method we developed, and profile their contents to identify and improve upon biomarkers indicative of prostate cancer aggressiveness. Such EV biomarkers could help physicians and patients more confidently make appropriate treatment decisions.

Now, a large number of prostate cancer (PrCa) patients is managed with surveillance (watchful waiting), including intermediate risk patients who have a significant risk for progression and metastasis. Our group studies cancer metabolism. We found that fat metabolism stimulates progression of PrCa and that well-tolerated treatments used for the treatment of inflammatory diseases and diabetes can slow down this progression. Currently, we lead a multi-center proposal for a clinical trial to investigate such medications. However, there is lack of good biomarkers to predict PrCa progression. Here we propose a pilot study to begin investigating whether gene expression and protein levels of enzymes of fat synthesis can predict progression in intermediate risk prostate cancer. If positive, this work will form a strong basis for future biomarker studies and may help develop a test to predict early which prostate cancer patients need early treatment or not.

Radiation therapy remains one of the most important treatment modalities for prostate cancer, however about 30% of men will experience adverse reactions– some near time of treatment, and others developing more slowly– that have the potential to limit treatment and/or irreversibly affect the patient’s quality-of-life. While improvements in the technical aspects of radiation therapy have the ability to limit the development of some of these toxicities, there is a large genetic component to the development of these effects that remains unknown, and an active area of prostate cancer research.  This project will assess whether selected genetic variants, which we can measure in a patient’s DNA sample, are associated with the development of long term adverse events, which are often irreversible and a source of substantial morbidity and decreased quality of life.  Being able to determine who might be at risk for developing the most challenging outcomes from care would allow physicians and patients to better understand and tailor treatment options for men with prostate cancer.

HDR brachytherapy is the most accurate and precise way of delivering an optimal radiotherapy dose to the prostate and has been shown to be associated with quality of life benefits in men receiving a combination of brachytherapy and external beam radiation compared to the alternative type of brachytherapy, the permanent seed implant. We want to expand the program to offer HDR brachytherapy to those men with earlier stage disease who do not require external beam radiotherapy as part of their treatment. We will use advanced imaging to localize the cancer within the prostate in order to give a higher dose to that site and we will introduce genetic testing of the cancer cells to determine if their inherent aggressiveness effects their response to brachytherapy.

Bone is the most common metastatic site for prostate cancer. Once these tumors have spread to bone, the cancer becomes incurable, thus we need to better understand how tumors get to and grow in the bone. Our team has shown that when we deplete a tumor cell surface protein, namely integrin β1 (ITGβ1), these tumor cells have an impaired ability to form bone metastases. We also have evidence that ITGβ1 is found in tumor-derived exosomes (EXs) and microvesicles (MVs). These are small membrane-bound particles that circulate throughout the body and are thought to ‘prime’ the new metastatic sites for tumor spread thereby facilitating metatatic growth. As ITGβ1 binds collagenI, a major component of bone, we hypothesize that ITGβ1-containing EXs/MVs preferentially localize to bone as a result of their binding to collagenI. Here they modify bone cells to more readily support the growth of the tumor once it arrives in the bone. We will test our hypothesis with well-established models of bone metastasis, and determine the mechanism by which ITGβ1 enhances bone metastasis and whether ITGβ1 blockade is a rational therapeutic strategy to prevent bone metastasis growth and progression.

Painful bone metastases are common among patients with prostate cancer and a mainstay in their treatment is palliative radiation therapy (RT). When RT is directed to bone metastases adjacent to the small bowel and abdominal organs it frequently induces nausea and vomiting; two of the most feared symtpoms associated with anti-cancer therapies. The drugs most commonly used to prevent RINV do so by blocking the serotonin that is released from the small bowel after RT damage, and preventing it from activating nausea and vomiting trigger zones in the brain. However, prolonged use of these drugs can cause constipation, dizziness and headache, they are costly, and animal studies suggest they are not effective beyond the first few RT treatments. Patients should not be receiving them for weeks at a time if they are unhelpful and toxic. We aim to prospectively follow patients receiving palliative RT for bone metastases to record their symptoms and measure biomarkers for serotonin release in the urine daily in order to determine the role of serotonin in the development of RINV throughout an entire course of palliative RT.

Our goal is to identify new treatment strategies through the identification of new combinations of agents to enhance chemotherapy response with the ultimate goal of providing clinical benefit to prostate cancer patients with these treatments. Currently, the response rates for chemotherapy in advanced disease that is resistant to standard therapies is poor. Enhancing the activity of chemotherapy and/or identifying markers that can predict response so that patients unlikely to respond to chemotherapy avoid toxicities without benefit and can be offered other therapeutic choices are urgently required. In this study, we are evaluating the potential of a cellular stress pathway as a target for therapy in combination with chemotherapy and whether it can also predict response to these important clinical agents.

We plan to open an Advanced Prostate Cancer Clinic to improve care for the growing number of men who suffer from advanced prostate cancer. This clinic will be unique and will provide services not currently offered in our region. The opening of this clinic provides a great opportunity to establish a research program focused on men with prostate cancer. This research program will help measure if patients in our region are receiving the best new drugs and correct diagnostic tests (like CT scans and MRI). The research program will also allow us to offer more cutting edge treatments through increased access to clinical trials. Research performed through this clinic will directly and immediately impact patients in a positive way.

This project aims to utilize tissue based markers to assess whether they can be utilized clinically in men diagnosed with prostate cancer to allow for better knowledge of the degree of aggressiveness or indolent of someone’s prostate cancer. the hope is that we can incorporate those markers in men seeking prostate cancer therapy to help doctors decide whether to offer active surveillance or definite therapy for individual patients. Currently there is about 30% chance that someone in active surveillance program will show disease progression due to in accuracy in identifying men with aggressive disease based on biopsy parameters.

Cisplatin, one of the most potent and widely used anticancer drugs, is being evaluated for chemotherapy of advanced metastatic prostate cancer where hardly any effective treatment options exist. The focus of our research is on the mechanism of cisplatin detoxification by the Wilson disease protein (ATP7B) and interplay between various copper transporters in the pathways of cisplatin delivery to the target on the one hand, and drug detoxification on the other. The goal of this project is to investigate if copper carrier Atox1 potentiates pharmacological activity of cisplatin by delivering it directly to DNA in the cell nucleus, and to determine the role of copper transport proteins in modulating prostate cancer sensitivity to cisplatin. Our investigation of the interplay between copper and platinum transport in the cell will lead to more effective and less toxic chemotherapy protocols for treating advanced prostate cancer with platinum drugs.

Prostate cancer (PC) is the second leading cause of cancer death in men. Radiofrequency ablation (RFA) is a new therapeutic procedure leading to tumor ablation. Although RFA prolonged patient’s survival, its major drawback is the incomplete tumor ablation leading to disease recurrence and patient’s death. In immune system, CD8+ cytotoxic T lymphocytes (CTL) play a critical role in fighting against tumor. In this study, we will perform in vitro experiments to identify optimal temperatures leading to PC apoptosis of heat-treated PC cells, and will develop an experimental RFA protocol in our animal model bearing mouse PC for improvement of in vivo RFA-induced beneficial anti-PC CTL responses through identification of optimal RFA-generated temperatures. Finally, the optimal experimental RFA protocol resulting in both efficient PC ablation and potent anti-PC CTL responses to reduce PC recurrence will be used as a guideline to establish an optimal clinical RFA protocol for PC therapy applied

The prostate specific antigen (PSA) blood test is used as a prostate cancer screening test for men in Saskatchewan. However, an abnormal PSA test causes a large number of men to have a prostate biopsy that turns out to be negative (i.e., false positive). With a partnership between researchers and clinicians from the Regina Qu’Appelle Health Region, London Health Sciences Center, Cypress Hills Health Region and the Saskatchewan Cancer Agency, we are studying whether a new blood test called “prostate cancer microparticle test” in men screened for prostate cancer can accurately identify aggressive prostate cancer. The test measures small pieces of tumour that are released into the blood when the tumour grows. It is hoped that this test could better identify men who are at risk for clinically important prostate cancer so they can receive timely and appropriate treatment.