Bladder cancer is the fifth most common cancer in Canada, with 12,300 Canadians diagnosed in 2023. Smokers, men and older adults are at a higher risk, and numbers are expected to rise as our population ages.
“Treating bladder cancer is costly, resource intensive and often unsuccessful,” explains Dr. Madhuri Koti, associate professor in the department of biomedical and molecular sciences at Queen’s University. There is an urgent unmet need for biomarkers and novel therapeutics for the treatment of early-stage bladder cancer. “That’s why we are so excited that the Terry Fox Research Institute has chosen to invest in our research.”
The multidisciplinary team is also thrilled to be selected as a new Terry Fox Program Project Grant and will use their $2.4 million of multi-year funding to address the question of why the primary therapy used to treat this cancer in the early stages works for some patients and not others. BCG – or Bacillus Calmette Guérin – therapy is the primary treatment for early-stage bladder cancer, particularly for patients predicted to be at higher risk of progression. Through this PPG, the team will focus on gaining a deeper understanding of how BCG therapy stimulates the immune system’s anti-tumour response in some patients and fails in others.
This unique immune-boosting therapy was developed at Queen’s University nearly 50 years ago and is now used globally. It involves administering the BCG vaccine – the same vaccine used to prevent tuberculosis – directly into the bladder after the tumour is surgically removed to clean up any remaining cancer cells. This helps to prevent tumour progression or recurrence of the disease and helps avoid the need for bladder removal.
"Unfortunately, more than half of patients do not benefit from this treatment. Recurrence and progression following BCG treatment remain significant challenges," says Dr. Koti. “We want to identify early on which patients are unlikely to respond so they can be treated with alternative therapies.”
The team will take a unique, integrated approach, using patient-derived tumours, cell-based models and animal models, to explore the dynamic interactions that occur as the immune system responds to cancer throughout disease progression.
This PPG includes three projects as well as a core that will provide technological and data analysis support.
- The first project is led by Drs. David Berman and Lynne-Marie Postovit. The team will focus on identifying what makes bladder cancer cells able to adapt and resist treatment – a process known as cell plasticity. The team will study tumours prior to and during disease progression in those patients who do not respond to BCG therapy to learn how they adapt to the selective pressure of the immune environment and progress.
- In the second project, led by Drs. Madhuri Koti and Robert Siemens, a detailed immune profiling of tumours at the time of initial surgery and those at the time of recurrence and progression, will be conducted. A combination of artificial intelligence-based methods and spatial immunophenotyping imaging approaches developed by Dr. Kathrin Tyryshkin and Dr. Sonia del Rincon (McGill University), will be used to identify predictors of disease outcome. Chemical engineers Drs. Carlos Escobedo and Laura Wells, on this team will also help develop a novel test for immune response monitoring during BCG therapy.
- The project three team constituted by Drs. Charles Graham, Peter Greer and Andrew Craig, will examine patients’ immune cells in the blood and aims to discover newer immune memory responses underlying patients’ responsiveness to BCG therapy. Using animal models, the team will also examine the influence of novel immune suppressive proteins on response to BCG.
Advanced computational analytics of data generated through these projects will be supported by a team led by Drs. Amber Simpson and Tricia Cottrell.
“This funding from the Terry Fox Research Institute allows us to bring diverse aspects of our independent research initiatives, strengthen national and international collaborations, and most efficiently utilize patient-derived material and expertise and build a world-class, internationally recognized Bladder Cancer Research Program at the Sinclair Cancer Research Institute” says Dr. Koti.
In addition to advancing scientific knowledge, the grant will play a critical role in training the next generation of researchers.
"This program is unique in that it allows trainees to learn from each other's projects and apply that knowledge. We aim to equip them with the tools needed to carry this research forward, with the hope of reducing the incidence and recurrence rates of bladder cancer, ultimately improving the lives of these patients."
Dr. Koti expresses her gratitude – on behalf of her entire team – to everyone who supported this Terry Fox research grant, including donors to the Terry Fox Foundation who have raised funds for this cancer research in Canada.
“We are extremely honoured at Queen’s to be awarded this PPG and to continue research on a treatment that started here more than 50 years ago,” she says. “A huge thank you to everyone who supported this important work.”