2020/201 Bladder Cancer Canada Grant Recipients

We are pleased to announce two recipients for the Bladder Cancer Canada Research Grant this year! Dr. Bernie Eigl (University of British Columbia) and Dr. Peter Black (University of British Columbia) will each receive a $50,000 grant for their projects, for a total of $100,000. Please see below for more information on each project.

ctDNA-FGFR status as a predictive biomarkerfor FGFR targeted therapy
(Dr. Bernie Eigl)

Bladder cancer is the 10th most common cancer, affecting almost 12,000 Canadians each year. Although advanced disease is still incurable, new therapies have recently become available that are significantly improving outcomes. One of these is a class of medications that block the activity of a gene called FGFR which promotes cancer growth. These medications are only effective in the roughly 20% of patients who have mutations in FGFR genes.

Currently, the test for FGFR mutations is performed on tissue samples obtained at surgery or from a biopsy, but this archival tissue may not be truly representative of the cancer currently progressing in a patient. Our group has recently shown that bladder cancer DNA can be isolated from a patient’s blood sample and that this testing method accurately reflects the mutations found in tissue.

This project is looking at whether a blood test can provide a more timely and accurate assessment of FGFR mutations, thereby providing this treatment to those who are most likely to benefit from it. Answering this question will require participation of a large number of bladder cancer patients from all across Canada. This grant will provide the necessary support to bring together cancer centres from across the country to collect blood samples for testing. It will also allow us to learn more about the way cancers may become resistant to these treatments, as we will also analyze patient blood samples when their cancers progress.

Computer-aided Discovery of a Specific Inhibitor of Notch-2 in Bladder Cancer
(Dr. Peter Black)

Bladder cancer (BCa) remains the 5th most common malignancy in Canada. Despite optimal management, which may include chemotherapy and surgical removal of the bladder, only ~50% of patients with muscle-invasive disease survive 5 years. Recent advances in immunotherapy are changing the way in which we treat the disease, but evidence shows that only a small proportion of patients benefit with durable responses. Immunotherapies are also associated with high cost and side effects, and some patients are not eligible to receive them.

An unmet clinical need therefore exists for alternative molecules that circumvent these limitations. The importance of Notch in BCa is well-described. We have shown that Notch2 (N2) drives cancer growth and is a promising target for the development of novel drugs. Here we propose to characterize novel inhibitors specific to N2 that utilize mechanisms of action that differ from those of other inhibitors, such as gammasecretase inhibitors, which target all Notch receptors and often have off-target effects, or more specific monoclonal antibodies, which are challenging and costly to manufacture.

In our first aim, we describe the use of a computer-aided approach to select candidate inhibitors from existing libraries. In the second aim, we will screen those molecules in cell culture for their ability to inhibit N2 specifically. In our third aim we will characterize promising molecules functionally. Lead candidates identified here will require further optimization with the goal of developing an agent to control bladder cancer growth, and thereby enhance patient survival and quality of life.

Congratulations to Dr. Eigl and Dr. Black on receiving these grants, and we wish them all the best in their research! We look forward to reporting back to you on their research outcomes in the future.

Congratulations to Dr. Bernie Eigl (left) and Dr. Peter Black (right) for their successful applications!

2019/2020 Bladder Cancer Canada Grant Recipients

We are pleased to announce two recipients for the Bladder Cancer Canada Research Grant this year! Dr. Wassim Kassouf (McGill University) and Co-Investigators, Dr. Girish Kulkarni (University of Toronto) and Dr. Rodney Breau (The University of Ottawa) will each receive a $50,000 grant for their projects, for a total of $100,000.

Dr. Kassouf’s grant will be used to study combination therapy and its systemic effects on immune memory. Does the combination of radiation plus PD-L1 blockade induce immunological memory in muscle invasive bladder cancer? Findings from this research will have important clinical relevance as it provides evidence for sustained clinical response of combination therapy, which will have a positive impact in survival and quality of life of MIBC patients.

Drs. Kulkarni and Breau will conduct their study to determine the feasibility of randomizing patients to chemotherapy prior to surgery versus surgery alone. The project will focus on a rare form of urothelial cancer called upper tract urothelial carcinoma, which affects the lining of the kidney and the ureter. Eventually, if successful, the study would be expanded to evaluate the impact of neo adjuvant chemotherapy on survival.

Congratulations to Drs. Kassouf, Kulkarni and Breau on receiving these grants, and we wish them all the best in their research! We look forward to reporting back to you on their research outcomes in the future.

Left to Right: Drs. Wassim Kassouf, Girish Kulkarni and Rodney Breau

2018/2019 Bladder Cancer Canada Grant Recipients

Twenty-five percent of patients with bladder cancer are diagnosed with muscle-invasive disease.  These patients usually receive chemotherapy followed by surgery to remove the bladder.  Up to 60% of tumours, however, do not respond to chemotherapy.  This study aims to measure the abnormal biological pathways in bladder tumour tissue at the RNA and protein levels, and to identify the pathways responsible for resistance to chemotherapy.  This approach will allow Dr. Black’s research team to identify mechanisms of resistance to chemotherapy and, in the future, test drugs that block the identified resistance pathways.  If successful, this project will open the door to novel therapies to overcome chemo-resistance.

Pictured below (L-R): Gregg Morin, PhD (Head of Proteomics, BC Cancer Genome Sciences Centre); Lead Investigator – Peter Black, MD FRCSC (Professor, University of British Columbia); Josa Batista da Costa, MD (post-doc); Kenichiro Ikeda, MD PhD (post-doc)