Brain Cancer Canada has announced two significant research grants totaling $170,000 to University of Toronto investigators pursuing innovative approaches to combat glioblastoma, the most aggressive and treatment-resistant form of brain cancer. The funding supports complementary research strategies targeting different aspects of this devastating disease that claims the lives of more than 95% of patients within five years of diagnosis.
MicroRNA Research Targets Glioblastoma Stem Cells
Dr. Leonardo Salmena received $85,000 for his project "Exploring microRNA as Targets for Glioblastoma Therapy," which focuses on understanding and targeting glioblastoma stem cells (GSCs). These specialized cancer cells are believed to drive tumor growth and resistance to current therapies, representing a critical barrier to effective treatment.
"Our research is focused on unraveling the biology and vulnerabilities of key driver cells known as GSCs. Only by deeply understanding these cells can we hope to develop innovative therapies that effectively target and eliminate them," Dr. Salmena explained.
His team has identified several microRNAs—small, non-coding regulators of gene expression—that are critical for GSC growth and survival. The research aims to characterize these microRNAs' specific roles in regulating GSC behavior, with the ultimate goal of developing new therapies capable of overcoming treatment resistance.
Current treatments for glioblastoma are largely ineffective, partly due to the presence of GSCs. Despite their importance in driving the disease, significant gaps remain in understanding GSC biology, making Dr. Salmena's work particularly valuable for advancing the field.
Targeting Hypermutant Recurrent Tumors
The second grant supports Dr. Stéphane Angers' project "Discovery of Druggable Vulnerabilities in Hypermutant Recurrent Glioblastoma." This research addresses the challenge of recurrent glioblastoma tumors that emerge despite aggressive standard-of-care treatments including surgery, chemotherapy, and radiation.
Approximately 15% of recurrent glioblastoma tumors acquire mutations in the MSH6 gene, which drives resistance to chemotherapy and leads to hypermutation—a phenomenon characterized by the accumulation of numerous additional mutations. Dr. Angers' preliminary findings suggest that hypermutant glioblastoma cells may exhibit heightened sensitivity to antifolate drugs already approved for other clinical indications.
"Our discovery of a potential genetic vulnerability in tumor cells could mean that certain cases of recurrent glioblastoma are treatable with drugs already on the market for other conditions," Dr. Angers noted.
The project has two primary objectives: evaluating differences in drug sensitivity between hypermutant and non-hypermutant recurrent glioblastoma cells, and employing cutting-edge genetic screening techniques to identify additional therapeutic targets for this particularly resistant subset of tumors.
Addressing Critical Medical Need
Glioblastoma represents one of the most challenging cancers to treat, with fewer than 5% of patients surviving five years after diagnosis. The disease is the most common and lethal brain malignancy in adults, and effective drug targets for recurrent glioblastoma are currently lacking.
Both research initiatives represent important advancements in the field, offering promising paths toward more effective treatments for this devastating disease. The work could potentially change how clinicians think about and treat glioblastoma by targeting previously unexplored vulnerabilities in cancer cells.
Funding and Support
These grants were made possible through grassroots fundraising initiatives and memorial contributions from across Canada. Dr. Salmena's project received support from Run for Jayne, Move to Promote GBM, Ride for Don, Julia Coey Memorial, and Farands for the Fight. Dr. Angers' research was supported by contributions from Sault Ste Marie Warriors, Burpees for Brain Cancer, and memorial fundraisers for Bernardo Scalisi, Roxanne Tanton, and Greg McLane.
The announcements are part of a series of six grants announced during Brain Cancer Awareness Month. Since 2015, Brain Cancer Canada has directed more than $2.4 million to brain cancer research across 25 projects at nine institutions, research centers, and hospitals throughout Canada.
