2010 Clinician Scientist Awards

Name of person or group
Dr. Frederic Pouliot, Laval University
 
Name of program or research project
DD3/PCA3 promoter-dependent molecular imaging of prostate cancer local recurrence after radical prostatectomy using adenoviral mediated amplification systems
 
Investment and period of investment
$300,000 from 2010 to 2012
 
Outline of program or project
The prostate specific antigen (PSA) is a protein secreted by normal and cancerous prostate cells and that can be quantified in the blood of men .  After surgical removal of the prostate for prostate cancer (prostatectomy), the blood PSA levels should be undetectable.  When it persistently increases after prostatectomy, it indicates that there is a recurrence of cancer.  In this context, the main challenge for the clinician in the treatment decision is to determine if the recurrence of the cancer cells is locally in the surgical bed (pelvis) or in other organs ( this is called a metastasis).  Treatments for these two locations of cancer cells  are different: radiation therapy is administrated for local recurrence and hormonal therapy is kept for metastasis.  Currently, there is no good imaging technique to assess the location of the prostate cancer cells and therefore, success of treatments are poor for this clinical condition. 

We propose to develop a new molecular imaging technique to detect specifically prostate cancer cells in the surgical bed after prostatectomy in mice models. 

To detect prostate cancer cells, we will construct a virus that can image specifically prostate cancer cells that express the DD3 gene, a gene specifically expressed in prostate cancer cells (DD3-virus).  We will also construct a slightly different virus that can treat specifically prostate cancer cells in order to prevent recurrence of the disease after prostatectomy. The proposed experiments will be done in the mouse models.  

The DD3-virus will detect malignant prostate cells but not benign prostate cells in vivo.  The DD3-virus will also prevent local recurrence, metastasis and will increase overall survival after tumorectomy in the mouse.  

Impact on prostate cancer prevention and treatment:  The dual imaging and therapeutic potential of the DD3-virus might lead to the development of new molecular imaging/treatment tools to detect and treat specifically prostate cancer cells in the clinics and therefore, better assign personalized treatments in the context of PSA-recurrence after prostatectomy.


 
Name of person or group
Dr. Urban Emmenegger, Sunnybrook Health Sciences Centre

Name of program or research project
Metronomic Chemotherapy in Castration-Resistant Prostate Cancer: Overcoming Treatment Resistance
 
Investment and period of investment
$300,000 from 2010 to 2012
 
Outline of program or project
Antiangiogenic drugs, a novel group of anticancer agents, impair the growth of tumor blood vessels, which results in tumor cell starvation. Many conventional chemotherapy drugs possess similar antiangiogenic effects, in particular when they are administered frequently, but at lower than usual doses. This novel form of chemotherapy use, termed metronomic chemotherapy, results in fewer side-effects than conventional chemotherapy and antiangiogenic drugs. The superior side-effect profile of metronomic chemotherapy is an advantage especially in elderly prostate cancer patients with a typically higher risk of treatment-related adverse effects. Unfortunately, treatment resistance limits the benefits of metronomic chemotherapy, as is the case with conventional chemotherapy. However, recent evidence indicates that the mechanisms of resistance to metronomic versus conventional chemotherapy are different.
 
By using human prostate cancer cells grown in mice treated with different metronomic chemotherapy regimens, Dr. Emmenegger’s research team intends to isolate resistant tumor cell variants. These cells will then be used to test whether resistance to a given chemotherapeutic drug also confers resistance to other chemotherapy agents when used in a metronomic manner. Furthermore, the properties of metronomic chemotherapy sensitive and resistant tumors will be compared, with the aim of finding markers that predict response to such therapy. Candidate markers will be studied in blood and tumor samples from prostate cancer patients.

Metronomic chemotherapy represents a novel and promising treatment strategy for the typically elderly patient with advanced prostate cancer. The findings of the outlined experiments are expected to help improve the benefits associated with metronomic chemotherapy in three major ways. First, they will provide information as to whether different chemotherapy agents can be successfully used one after the other in prostate cancer patients. Second, markers associated with response to metronomic chemotherapy could be useful to select patients most likely to benefit from such therapy. Finally, comparing treatment-sensitive and treatment-resistant tumors may ultimately prove informative to design strategies to overcome treatment resistance.




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