Research Grants 2007/2008

Dr. Tarek Bismar

Interaction of PTEN genomic deletions and TMPRSS2-ERG gene fusion in prostate cancer Progression.
Category: translational/early detection/disease progression
Institution: University of Calgary, Calgary, AB

Prostate cancer cells contain many alterations in their genetic material. Some of these alterations cause the loss of one or more genes (called a ‘deletion’). Another type of alteration is when two genes accidentally fuse beside each other (called a ‘fusion gene’). A recently discovered ‘fusion gene’ (named TMPRSS2/ERG) is thought to be associated with more aggressive forms of prostate cancer. However, research suggests that this fusion gene can’t make normal cells cancerous on its own.

Dr. Bismar’s laboratory will study the interaction between the TMPRSS2/ERG fusion gene and another gene called PTEN, which is commonly lost (deletion) in prostate cancer and is linked to the development and progression of more aggressive disease. Data from these studies may allow physicians to identify patients with high risk of disease progression early on, so they can be targeted more effectively before their cancers advance.

Dr. Robert Bristow

DNA repair inhibition in prostate cancer cells as a means of individualizing cancer therapy Category: translational/therapeutics
Institution: Princess Margaret Hospital, Toronto, ON

DNA in a cell can be damaged by a variety of factors like radiation and UV light. Cells find and fix damage to the DNA in a collection of processes called DNA repair. Recent studies suggest that some prostate cancer patients have defects in the DNA repair processes, leading to an increased risk of developing cancer and perhaps more aggressive forms of the disease.

Dr. Bristow and his colleagues will study cells and tissues taken from prostate cancer patients to see if there are defects, in any of the seven different DNA repair mechanisms, that can be targeted by radiotherapy or chemotherapy treatment.

Using advanced microscopy techniques, they will watch the repair process in the cell directly after it has been hit with radiotherapy or chemotherapy. To confirm their findings from the laboratory, they will study actual prostate cancer tissues to see if the same defects exist in prostate cancer patients’ tumours. This study could lead to the creation of new diagnostic test which will help personalize treatments.

Dr. Rajiv Chopra

Transurethral MR elastography: A novel method for imaging prostate cancer 
Category: clinical/imaging
Institution: Sunnybrook Health Sciences Centre, Toronto, ON

Biopsies are used to diagnose prostate cancer. But they are not perfect and because they only examine samples of the prostate, they can sometimes incorrectly result in a cancer-free diagnosis in a man who has the disease. Imaging techniques that allow doctors to find and localize cancer by looking at the whole prostate could aid the process and result in more accurate diagnoses.

Dr. Chopra and colleagues will examine magnetic resonance elastography (MRE), a new technique that lets doctors see tissue stiffness. This study will test MRE in animals before assessing its practicality in men. MRE could provide a non-invasive way to find cancer. It could reduce the number unnecessary biopsies and make biopsies more effective by leading them to take samples from areas that are more suspicious.

Dr. Daniel J. Dumont

The role of angiopoietins in prostate cancer; identification of new biomarkers of tumour growth and metastasis
Category: basic science/therapeutics
Institution: Sunnybrook Health Sciences Centre, Toronto, ON

The formation of new blood vessels, called angiogenesis, is an important step in the transition of tumours from benign (non-cancerous) to malignant (cancerous). Angiogenesis involves many steps and many different types of cells and proteins. 

Dr. Dumont and his team will be focusing on a class of proteins called Angiopoietins and concentrating on two (Ang1 and Ang2) which are important players in the progression of cancer. Although we know that these angiopoietins are present in prostate cancer, their role is unknown. Dr. Dumont’s team will study the differences between the effects of Ang1 and Ang2 in their role in prostate cancer to determine which should be targeted for the treatment.

They will create an experimental model in mice that are known to develop prostate cancer, but also are exposed to Ang1 and Ang2. They will then analyze the influence of these angiopoietins on prostate tumour growth and metastasis. A better understanding of how these angiopoietins work could result in new treatments.

Dr. Gerardo Ferbeyre

A mouse prostate model of oncogene-induced senescence
Category: basic science/therapeutics/early detection
Institution: University of Montreal, Montreal, QC

Normal cells lose the ability to divide and this biological process is called Senescence. In malignant or aggressive cancer, this process of Senescence does not take place and cells divide in an uncontrolled way. (Benign tumours are tumours where Senescence stopped the tumour from growing).

Studying the process of Senescence is key to controlling cancer and preventing tumours from growing and spreading. Dr. Ferbeyre and his collaborators plan to create the first model of Senescence in the prostate. They will create a mouse model that expresses a gene called STAT5, which is important in the development of prostate cancer. Their model will allow them to turn the gene on and off and study its role in cancer development and spread. By understanding how Senescence works – or doesn’t work - in prostate cancer, they hope to better detect, prevent and treat the disease.

Dr. Neil Fleshner

A randomized double-blind study of combination vitamin E, selenium and lycopene vs. placebo in men undergoing radical prostatectomy for prostate cancer. 
Category: clinical/prevention/therapeutics
Institution: University Health Network, Toronto, ON

Dr. Fleshner’s study looks at whether antioxidants/micronutrients, including vitamins, can prevent prostate cancer or slow its growth. He and his team will give 48 men with prostate cancer either pill with Vitamin E, Selenium, and Lycopene, or a pill with no active ingredients (a placebo) daily for 6 – 8 weeks before surgery. Tissue from the prostate, collected during surgery, will be analyzed. Comparing tissue from the two groups of men, the researchers will look for the presence and alterations of certain molecular markers that affect tumour growth and shrinkage and prostate cancer aggressiveness. The size of the prostate tumours will also be assessed and compared to determine whether these compounds affect tumour size.

If this relatively small study finds significant differences in the prostate tissue of the two groups of men, a larger clinical trial would be the next step to determine whether antioxidants can be used as a main prevention method or a complement to surgery and radiation.

Dr. Wilfred Jefferies 

Regulation of antigen processing machinery in prostate carcinomas
Category: translational/therapeutics
Institution: University of British Columbia, Vancouver, BC

A strong immune system can prevent prostate cancer and help men recover after treatment. Cancer cells are very good at hiding themselves so that the immune system does not detect and fight them off. Dr. Jeffries and his team have identified key processes in the cell (called ‘pathways’) that are altered in cancer cells, allowing these cells to avoid immune detection, and as a result grow. In this study, they plan on altering these pathways in cancer cells in animal models, in order to help the immune system find them. With the immune system’s help, cancer treatments could be made even more effective.

Dr. Réjean Lapointe 

Understanding the immunosuppressive effects of androgen in prostate cancer
Category: translational/therapeutics
Institution: University of Montréal, Montreal, QC

Male sex hormones (androgens) not only help prostate cancer cells survive, they also weaken the immune system. This is important because as prostate cancer cells become more aggressive, the immune system in the prostate gets weaker. A team lead by Dr. Lapointe will examine the way androgens impact the immune system in cases of prostate cancer and will provide information that could lead to new treatment options that combine androgen deprivation therapy (also called hormone therapy) and therapies that boost the immune system.

Dr. Suresh Mishra

Autocrine mobility factor: A potential target for IGFBP-3 in prostate cancer
Category: basic science/therapeutics
Institution: University of Manitoba, Winnipeg, MB

The process of cell death is called apoptosis. Apoptosis is important because it allows the body to get rid of damaged cells (for example cells that have DNA mutations). When apoptosis does not work damaged cells can pile up and cause cancer. In addition, chemotherapy can stop working if apoptosis does not occur. Dr. Mishra’s lab has been studying a protein which inhibits cell growth and promotes apoptosis in cancer cells. This protein is called Insulin-like growth binding protein-3 (IGFBP-3). This project will study the way IGFBP-3 works and how it interacts with other factors involved in apoptosis. If this study can shed light on how to boost apoptosis, its findings could lead to better treatments and prevention methods.

Dr. Jehonathan Pinthus 

Adiponectin as a tumour suppressor of prostate cancer
Category: translational/prevention
Institution: Juravinski Cancer Centre, Hamilton, ON

Studies suggest that obesity increases the risk of aggressive prostate cancer. Fat tissue produces many hormones, including adiponectin. This hormone is only secreted from fat cells and has been shown to suppress tumour growth. Unfortunately, obese people have lower levels of this helpful hormone. In fact, several large studies have found lower adiponectin levels in prostate cancer patients, suggesting that obese men with low levels of adiponectin are more at risk of the disease.

In this study, Dr. Pinthus and his collaborators plan to investigate how adiponectin fights prostate cancer. In particular, they will look at how it suppresses toxic compounds (called oxygen radicals) and its influence on the production of a molecule called AMPK that is involved in suppressing cancer cell growth. Understanding how adiponectin effects prostate cancer cells may shed light on the link between obesity and prostate cancer and lead to new targets for treatment.

Dr. Terrence Ruddy 

Does androgen suppression treatment in prostate cancer reduce myocardial blood flow reserve?
Category: clinical/therapeutics
Institution: University of Ottawa, Ottawa, ON

Androgen deprivation therapy (hormone therapy) is a common treatment for prostate cancer. But some studies suggest suppressing androgens can result in side effects like weight gain, high cholesterol and increased risk of heart problems. Dr. Ruddy and his team will compare two groups of prostate cancer patients – one on hormone therapy and one taking treatments – to see if suppressing androgens results in a decrease in blood flow to the heart.

The study’s results could lead to the creation of non-invasive testing to identify men on hormone therapy who have negative heart related side effects and help make hormone therapy safer for men by decreasing the risk of heart problems.

Dr. Marianne Sadar 

Preclinical evaluation of IN06-08 compounds for treatment of advanced prostate cancer.
Category: basic science/translational/therapeutics
Institution: BC Cancer Agency, Vancouver, BC

When prostate cancer is very advanced and becomes androgen-independent, there are not effective treatment options left. Dr. Sadar’s laboratory recently found a family of small molecules that effectively fight androgen-independent prostate cancer in animal models. In this study they will finish testing these molecules to evaluate their feasibility for clinical trials. These molecules – if they prove effective on human patients – could be turned into new drugs that will delay and prevent the development of androgen independent prostate cancer.

Dr. Theo Van der Kwast 

Genomic characterization of clinically distinct pathways of prostate carcinogenesis
Category: clinical/therapeutics/diagnostics
Institution: University Health Network/ Toronto General Hospital, Toronto, ON

Prostate cancer researchers are on the look out for markers that can help them separate men with slow growing prostate cancer (who can be treated with active surveillance) and men with aggressive forms of the disease (who need to be treated with other forms of therapy right away).

Scientists recently found that genetic alterations in the PTEN gene are linked to aggressive disease while loss of a part of chromosome 5 is linked to slow growing prostate cancer. Both alterations rarely occur in the same tumour. The main focus of this project lead by Dr. Van der Kwast, is to demonstrate whether these genetic alterations are present in the different growth patterns of a single case of prostate cancer. This information could give doctors a “genetic signature” of the cancer at the early stages of the disease and help predict how the disease will progress.

Dr. Mark Trifiro 

Isolation and characterization of active AR-transcriptional complexes – new therapeutic targets 
Category: translational/therapeutics
Institution: SMBD-Jewish General Hospital, Montreal, QC

Androgen deprivation therapy (hormone therapy) is a treatment but not a cure. Eventually, tumours become resistant to hormone therapy and there is no treatment for this late stage of cancer, which is called androgen-independent prostate cancer.

The process of becoming resistant involves the androgen receptor. Dr. Trifiro and his team will examine the changes that occur in the androgen receptor in men who are becoming resistant to hormone therapy. In order to better understand how the androgen receptor acts on prostate cancer cells, they will also try to identify other factors that interact with the androgen receptor. From this work, they hope to find new molecular markers that can be used in prognosis, help direct treatment in individual patients, and lead to alternative strategies for treating advanced prostate cancer.

Dr. Jinyi Zhang

Studies of the Ese3 transcriptional regulator as a tumour suppressor in prostate cancer
Category: basic science/therapeutics/prevention
Institution: Samuel Lunenfeld Research Institute, Toronto, ON

Prostate cancer is highly associated with the increased production of a class of proteins known as transcription factors. These proteins play a major role in controlling the growth of cells and one in particular, called Ese3, appears to be responsible for suppressing cell growth. Although Ese3 is usually produced at very high levels in normal prostates, data from Dr. Zhang’s lab suggests that it is severely reduced in cancerous prostates.

Dr. Zhang will examine the way Ese3 functions in the cell, and explore how it is lost in prostate cancer. He will also try to reintroduce normal levels of Ese3 back into prostate cancer cells to determine how this protein influences the course and outcome of disease. Data from this work will shed light on the link between loss of Ese3 and development of prostate cancer; help Dr. Zhang determine if Ese3 is a possible target for treatment; and lead to new methods of prevention.





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