An international study led by a scientist at the University of Ottawa Faculty of Medicine is opening new frontiers in the fight against glioblastoma (GB), a devastating cancer behind the most malignant and treatment-resistant brain tumours in adults.
Glioblastoma has long challenged researchers to uncover the molecular machinery that fuels the relentless growth of its aggressive tumours. Now, this new research not only deepens our understanding of this disease but also highlights a promising target that could greatly inform the future of next-generation therapies.
“Glioblastoma is resistant to treatment because tumours adapt, recruit surrounding cells, and switch survival pathways,” says Dr. Arezu Jahani-Asl, Canada Research Chair in neurobiology of disease and an Associate Professor in the Department of Cellular and Molecular Medicine whose research program is centered on developing new therapeutic strategies for brain diseases.
“This work suggests a central ‘control node’ that influences multiple tumour-promoting processes at once.”
Dr. Arezu Jahani-Asl
— Associate Professor and Canada Research Chair in neurobiology of disease
“This study points to a coordinated signaling axis that sits upstream of several of those resistance mechanisms. That matters because while many past therapies targeted single downstream effects, this work suggests a central ‘control node’ that influences multiple tumour-promoting processes at once,” she says.
A central control system for tumour growth
In a field where breakthroughs are urgently needed, the Jahani-Asl team in collaboration with scientists based in Canada, Italy and the U.S. offers a compelling new direction. Their work was recently published in the medical journal Signal Transduction and Targeted Therapy.
Central to the new study is the ‘Oncostatin M receptor’ (OSMR), a protein that the Jahani-Asl team has revealed plays an important role in brain cancer. In glioblastoma, OSMR emerges as a critical driver of tumour progression, working in close partnership with a common mutation.
“People don’t have years to wait for incremental advances. The reality (of glioblastoma) drives us to look for breakthroughs that can truly change outcomes.”
Dr. Jahani-Asl
“OSMR is more than just another receptor—it behaves like an orchestrator of tumour progression,” Dr. Jahani-Asl explains. “It integrates signals from the tumour microenvironment to drive aggressive tumour cell states often linked to treatment resistance.”
The study also reveals that OSMR’s influence supports the survival and maintenance of brain tumour stem cells (BTSCs), a particularly dangerous cell population responsible for tumor recurrence and resistance to therapy. It does this by boosting the energy production systems cancer cells rely on to thrive under stress.
Unmasking a hidden molecular partner
Using an innovative technique, the ambitious research team mapped the full network of proteins that interact with OSMR. Among the most significant discoveries was the identification of “chloride intracellular channel 1”, CLIC1 for short, as a crucial regulator within this network.
“CLIC1 is a bit of a ‘hidden player’ that’s gaining attention,” Dr. Jahani-Asl says. “Think of CLIC1 as a molecular switchboard that helps tumor cells manage stress, movement, and survival. This study links it directly to OSMR-driven tumor behavior and highlights a tumour-associated membrane form as a potential therapeutic target.”
The implications of this finding are significant.
When CLIC1 is genetically deleted, the entire signaling system begins to collapse. The result is a measurable slowdown in glioblastoma progression, underscoring how vital this channel is to sustaining key pathways in the disease.
Using advanced electrophysiological techniques, the team has also broken new ground by exploring the biophysical properties of this mysterious channel. The researchers revealed a previously unknown bidirectional relationship: OSMR regulates CLIC1 function, while CLIC1, in turn, supports OSMR-driven signaling. This crosstalk creates a self-reinforcing system that fuels glioblastoma’s aggressive behavior.
“Our work shows that OSMR–CLIC1 crosstalk is required for signal transduction,” she says. “We have also mapped the interaction domain in order to design small peptides to halt this key oncogenic pathway. Instead of tumours being chaotic, this research suggests they may rely on key ‘conductors’ like OSMR to organize their growth and defense strategies.”
Forging a promising path toward future therapies
Perhaps the most exciting aspect of this work lies in its future therapeutic potential.
The researchers tested an antibody designed to specifically target the transmembrane form of CLIC1. They were able to disrupt the critical signaling pathways that drive tumour growth.
This suggests a possibly effective strategy for eventually weakening glioblastoma at its very core.
Looking ahead, the team plans to validate the findings across multiple glioblastoma subtypes to better understand which patients may benefit most from therapies targeting the OSMR–CLIC1 axis. Future work will also focus on designing treatments that disrupt OSMR–CLIC1 interactions and evaluating their safety through various studies, both alone and in combination with current standards of care.
Driven by the urgency facing patients and families
As research continues, the urgency of this work extends far beyond scientific discovery for Dr. Jahani-Asl, who is a member of the Brain and Mind Institute at the uOttawa Faculty of Medicine.
“Working on glioblastoma, you see how fast it progresses, how limited the options are, and how it affects not just patients but entire families—emotionally and practically. People don’t have years to wait for incremental advances.”
“That reality drives us to look for breakthroughs that can truly change outcomes,” she says.