Researchers at UHN’s Princess Margaret Cancer Centre (PM) showed that mutations in a key pathway (the KEAP1/NRF2 pathway) can drive radiotherapy resistance in head and neck squamous cell carcinomas (HNSCC)—a group of cancers that develop from the cells that line the moist surfaces of the head and neck.
For many solid tumours, including HNSCCs, a type of radiation therapy given from outside the body (external beam radiation) is usually the standard treatment, often combined with chemotherapy. Radiotherapy uses high-energy radiation to kill cancer cells. Understanding why some tumours resist radiation treatment is crucial for improving patient outcomes and reducing disease-related complications.
Approximately 20% of HNSCCs involve mutations in a specific set of genes that form the KEAP1/NRF2 pathway. This pathway typically helps protect cells from damage caused by reactive oxygen species—unstable oxygen molecules that can damage DNA and other cell parts. A key way that radiation therapy works is by generating these reactive oxygen species to kill cancer cells. Mutations in this pathway have previously been linked to a poor response to standard cancer therapies, including radiation therapy.
To investigate this further, the research team, co-led by PM’s Dr. David Kirsch, created specialized experimental models and cell lines that mimic the genetic changes seen in human cancers. They also exposed models to cancer-causing chemicals found in tobacco to mimic real-world environmental risk factors. Tumours were then examined using a variety of lab techniques, and radiation therapy was administered to see how changes in the KEAP1/NRF2 pathway affect both treatment resistance and the immune system’s response.
The team found that tobacco chemicals accelerate the initiation and growth of head and neck tumours. In addition, they found that reduced KEAP1 activity resulted in tumours with stronger NRF2 activation, increased resistance to radiation treatment, more blood vessels feeding the cancer, suppressed immune system function, and reduced survival.
The findings highlight a critical link between genetic changes to the KEAP1/NRF2 pathway and treatment resistance in head and neck cancer. Ongoing studies aim to understand this pathway better and to develop new ways to make radiation treatment work more effectively in people whose cancers carry these genetic changes.
Dr. Rutulkumar Patel, Assistant Professor at Baylor College of Medicine, is the first author of the study.
Dr. Yvonne M. Mowery, Associate Professor of Radiation Oncology at UPMC Hillman Cancer Center, is a co-senior author of the study.
Dr. David Kirsch, Senior Scientist at Princess Margaret Cancer Centre (PM), Allan Slaight Scientist at PM, Peter and Shelagh Godsoe Chair in Radiation Medicine, and Professor in the Departments of Medical Biophysics and Radiation Oncology at the University of Toronto, is a co-senior author of the study.
This work was supported by the National Institutes of Health, the American Cancer Society, the National Cancer Institute, Veterans Affairs (USA), the National Institute of Allergy and Infectious Diseases, the Cancer Prevention and Research Institute of Texas (CPRIT), and The Princess Margaret Cancer Foundation.
Dr. Yvonne Mowery has leadership roles in ASTRO and NRG Oncology, receives grant funding from the National Institutes of Health, the Damon Runyon Cancer Research Foundation, and Stand Up to Cancer (SU2C), and receives an honorarium from the University of Wisconsin-Madison.
Dr. David Kirsch reports grant funding from the National Cancer Institute (NCI), in support of the research described in this manuscript. In the past, he has received support from the Merck Investigator Studies Program, SU2C, Bristol Myers Squibb, Varian Medical Systems, and the Department of Defense. He also receives other National Institutes of Health (NIH) funding not related to this work. Dr. Kirsch holds a license for an imaging device through Lumicell Inc., and patents through Lumicell Inc. and XRad Therapeutics. He served on the Scientific Advisory Board of Lumicell Inc., and holds stock in XRad Therapeutics and Lumicell Inc.
See the manuscript for the complete list of competing interests.
Patel R, Saab K, Luo L, Ma Y, Osman RA, Williams NT, Everitt J, Zelazowski MJ, Castro P, Decker WK, Hudson WH, Myers JN, Sandulache VC, Frederick MJ, Mowery YM, Kirsch DG. Nrf2 hyperactivation as a driver of radiotherapy resistance and suppressed anti-tumor immunity in head and neck squamous cell carcinoma. Clin Cancer Res. 2025 Jul 31. doi: 10.1158/1078-0432.CCR-25-0112. Epub ahead of print.
Two researchers from UHN’s Princess Margaret Cancer Centre are recipients of the 2024 Canadian Cancer Society Awards for Excellence in Cancer Research. Congratulations to Senior Scientists Dr. John Dick and Dr. Cheryl Arrowsmith on this achievement.
● Dr. John Dick – 2024 Lifetime Contribution Prize: This prize celebrates investigators who have enhanced the Canadian cancer research landscape beyond traditional research accomplishments—leading to significant benefits for people in Canada affected by cancer—and who are committed to passing that legacy on to the next generation of cancer researchers.
Dr. John Dick is a Senior Scientist at Princess Margaret Cancer Centre, a Professor in the Department of Molecular Genetics at the University of Toronto, and holds both the Helga and Antonio De Gasperis Chair in Blood Cancer Stem Cell Research and the distinction of University Professor at the University of Toronto. Dr. Dick has spent a lifetime studying how cancer works. His accomplishments range from discovering the cells that give rise to leukemia to developing new cancer treatments and finding ways to measure their success. He generated the first system for effectively studying human stem cells in the lab, enabling him to uncover how human blood develops and identify the unique stem cells that lead to cancer. His work has revealed processes that can be targeted by new drugs to stop cancer and prevent relapse.
● Dr. Cheryl Arrowsmith – Robert L. Noble Prize: This prize recognizes the outstanding achievements of Dr. Arrowsmith in biomedical cancer research.
Dr. Arrowsmith is a Senior Scientist at Princess Margaret Cancer Centre, a Professor in the Department of Medical Biophysics at the University of Toronto, and Chief Scientist at the Structural Genomics Consortium Labs affiliated with UHN and the University of Toronto. Dr. Arrowsmith studies how genes and proteins work together in cancer, with a focus on how genes are controlled in the human body—a process called epigenetics—and how the proteins that influence this control interact to drive cancer. She also develops chemical probes to study these proteins and identify potential targets for new anticancer drugs. Her work has provided essential drug discovery tools for the scientific community. She is also a strong advocate for new drug discovery and development, as well as a mentor and supervisor to many trainees.
Read the full story here.
The Royal Society of Canada (RSC) announced this year’s newly elected Fellows and incoming class of the RSC College.
The RSC is the nation’s pre-eminent organization of scholars, researchers, and artists. It celebrates excellence, promotes research, and provides independent advice on matters of public interest while fostering collaboration and mentoring future leaders to advance knowledge in Canada and beyond.
Congratulations to the following UHN researchers elected to the RSC:
● Dr. Shaf Keshavjee (Fellow) is a Senior Scientist, Director of the Latner Thoracic Laboratories, Chief of Innovation, and Co-Director of the AI Hub at UHN. He is a Professor of Thoracic Surgery and Biomedical Engineering at the University of Toronto, and is the Donald K. Jackson Chair in Lung Transplant Research. Dr. Keshavjee’s work has transformed lung transplantation through the development of the Ex Vivo Lung Perfusion (EVLP) system, which has doubled the number of lungs available for transplant. His research focuses on understanding the molecular mechanisms of lung preservation, injury, and repair related to transplantation. His team at UHN is developing diagnostics and therapies, including gene therapy and genome editing technologies, to further enhance lung repair.
● Dr. Bo Wang (Member of the College) is a Senior Scientist and the Chief AI Scientist at UHN, as well as a tenured Associate Professor in the Departments of Computer Science and Laboratory Medicine & Pathobiology at the University of Toronto. Dr. Wang’s research focuses on machine learning, computational biology, and computer vision, with an emphasis on developing novel machine learning algorithms to address clinical applications in biomedicine. His work has made significant contributions to these fields.
Over a hundred new Fellows were elected and recognized for their impactful achievements in the arts, social sciences, humanities, and sciences. The RSC also welcomed 59 new Members to the RSC College; the College consists of mid-career researchers who help the RSC address major challenges and seize opportunities in emerging fields in Canada and around the world.
Read the press release for award details and additional information about the upcoming ceremonies honouring the awardees.
UHN’s Summer Training and Research (STAR) Program celebrated its students through STAR Research Day—an opportunity for students to share their research experiences via engaging poster presentations.
Research Day marks the culmination of the STAR Program, a comprehensive summer research initiative led by UHN’s Office of Research Trainees (ORT). The program provides summer students the chance to participate in cutting-edge research while gaining essential professional development skills in research design and integrity, scientific communication, networking, and career exploration in science and health care.
At this year’s Research Day, held on August 7, 2025, 123 students presented posters. An additional 22 students shared their work virtually using the online platform VoiceThread. The poster competition, adjudicated by UHN graduate students, postdoctoral researchers, and staff, recognized five students for outstanding posters:
● Nicole Wiesner — supervised by Dr. Andrew McPartlin
● Isabella Gouthro — supervised by Dr. Chung-Wai Chow
● Alexander Ball — supervised by Dr. Kathryn Howe
● Allona Kaye Lim supervised by Dr. Ivan Yeung
● Sunny Yun – supervised by Dr. Suneil Kalia
In total, 107 students completed the STAR Program, marking a summer of growth, innovation, and community building within UHN’s dynamic research environment.
A new study, published in The Lancet Oncology, from a research team at UHN’s Princess Margaret Cancer Centre (PM) found that grading of meningiomas may be improved by evaluating the expression of the telomerase reverse transcriptase (TERT) gene.
Meningiomas are tumours that come from the membranes that surround the brain and spinal cord, called the meninges. Doctors grade these tumours by assessing a sample of the tumour, called a biopsy, under a microscope and determining how aggressive they look. Unfortunately, sometimes meningiomas behave more aggressively than they appear during the grading process.
The TERT gene produces a protein that is important for helping cells divide and grow by maintaining chromosome stability. In healthy cells, this gene is typically inactive; however, in cancer, it can become reactivated, allowing tumour cells to grow unchecked. For some meningiomas, a mutation in the TERT promoter gene—which regulates TERT expression—has been found to be behind the more aggressive behaviour of tumours. In meningiomas that express TERT, the TERT promoter gene may be either wildtype, meaning unmutated, or mutated in a way that increases gene activity and TERT expression. However, until now, studies have mainly explored the effect of TERT promoter mutations on meningioma prognosis, while the role of TERT expression outside of the mutated form remains largely unknown. “Up to one-third of meningiomas express TERT, while only 10% of these tumours have a TERT promoter mutation,” explains Dr. Farshad Nassiri, one of the study’s co-senior authors, on a recent episode of a podcast hosted by The Lancet Oncology.
To address this gap, the PM research team analyzed data from 1,241 meningiomas across eight international cancer care centres. They found that TERT expression—regardless of whether the gene is mutated or not—is associated with poorer prognosis, including reduced progression-free survival.
Further, the study revealed that meningiomas that expressed TERT, regardless of whether the gene was mutated or not , resembled TERT-negative tumours without TERT expression that are graded a full level higher. "For example, grade two tumours with TERT expression had progression-free survival resembling that of TERT-negative grade three tumours," explains Dr. Gelareh Zadeh, co-senior author of the study.
“Grading is an essential part of the process of planning treatment,” says Dr. Chloe Gui, the study’s lead author. “If we incorporate TERT expression into grading criteria, we may be able to more reliably identify meningiomas with aggressive clinical behaviour and offer treatment that better aligns with how the tumour behaves.”
Although the biological mechanism by which TERT contributes to cancer progression remains unclear, these findings suggest that TERT expression may serve as a valuable biomarker for improving the accuracy of meningioma grading and guiding more personalized treatment strategies.
The first author of this study is Dr. Chloe Gui, a neurosurgery resident and PhD candidate in the Surgeon Scientist Training Program at the University of Toronto and Macfeeters-Hamilton Neuro-Oncology Program at PM.
Drs. Farshad Nassiri and Gelareh Zadeh are co-senior authors of this study. Dr. Nassiri is a Scientist at PM, a neurosurgeon at UHN in the Sprott Department of Surgery, a neurosurgeon at Toronto Western Hospital, and an assistant professor in the Faculty of Medicine at the University of Toronto. Dr. Zadeh is an Affiliate Scientist at PM, a neurosurgeon and the Chair of Neurosurgery at the Mayo Clinic, and the former Dan Family Chair of the Division of Neurosurgery at the University of Toronto.
This work was supported by the Canadian Institutes of Health Research (CIHR), Brain Tumour Charity UK, Mary Hunter Meningioma Research Fund, V Foundation for Cancer Research, National Institutes of Health (NIH), and UHN Foundation.
For a full list of conflicts, see the publication.
Gui C, Wang JZ, Patil V, Landry AP, Singh O, Castelo-Branco P, Tabori U, Aldape K, Behling F, Barnholtz-Sloan JS, Horbinski C, Tabatabai G, Ajisebutu A, Liu J, Patel Z, Yakubov R, Kaloti R, Ellenbogen Y, Wilson C, Cohen-Gadol A, Tatagiba M, Holland AC, Sloan AE, Chotai S, Chambless LB, Gao A, Makarenko S, Yip S, Nassiri F*, Zadeh G*. The International Consortium on Meningiomas (ICOM). Analysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study. Lancet Oncol. 2025 Sep; 26: 1191–1203.
*Contributed equally as senior authors to this work.
Health disparities—often driven by social, economic, and demographic factors such as race—can lead to unequal access to care and poorer health outcomes. Researchers from The Institute for Education Research at UHN investigated surgical outcomes among Black and White urologic cancer patients and found that Black patients experienced more complications after surgery, despite having similar survival rates.
Analyzing data from over 28,000 patients in a national surgical database, the research team, led by first author Dr. Alex Bak, matched and compared individuals by procedure type, demographics, and medical history. Black patients were more likely to experience complications such as unplanned hospital readmissions, reduced kidney function, and cardiac arrest compared to White patients. Interestingly, Black patients were also less likely to be diagnosed with heart attacks or certain infections, including surgical wound infections.
These findings suggest that racial disparities in surgical recovery may be influenced by a combination of patient health factors, health care provider practices, and systemic barriers, such as limited access to specialized care or consistent follow-up support. Lack of access to high-volume surgical centres, where outcomes are typically better, may also contribute to these differences.
The study highlights the need for targeted interventions to improve surgical outcomes for racialized populations. Future research will explore how hospital referral patterns and access to high-volume surgical centers may shape these differences. By addressing these gaps in care, health systems can move toward more equitable outcomes for all patients undergoing urologic cancer treatment.
Dr. Alex Bak, first author of the study, is an anesthesiology resident at the University of Toronto.
Dr. Jason Lee, senior author of the study, is a Clinician Investigator at The Institute for Education Research at UHN. Dr. Lee is also an Associate Professor in the Department of Surgery at the University of Toronto
This work was supported by UHN Foundation.
Bak AB, Pace KJC, Gao B, Wallis CJD, Lee JY. Association of race and 30-day postoperative complications after urologic oncology surgery. Can Urol Assoc J. 2025 Jul 8. doi: 10.5489/cuaj.9201. Epub ahead of print.
Three UHN researchers were elected as Fellows of the Canadian Academy of Health Sciences (CAHS). As one of the highest honours in Canadian health sciences, Fellows are nominated from all disciplines and recognized for their excellence in advancing academic health sciences.
Congratulations to the following UHN researchers, who were among the 47 newly elected Fellows:
● Dr. Laura Dawson is a Clinician Investigator at UHN’s Princess Margaret Cancer Centre. Her research focuses on implementing advanced radiation technologies and exploring innovative therapeutic combinations to improve outcomes and minimize the side effects of radiation therapy, with a particular emphasis on liver cancers.
● Dr. Natasha Leighl is the Division Head of Medical Oncology and Hematology and a Clinician Investigator at UHN’s Princess Margaret Cancer Centre. Her primary area of research is the development of novel treatments for lung cancer, including targeted and immune-based therapies, and incorporating novel diagnostics such as liquid biopsy into patient care.
● Dr. Milica Radisic is a Senior Scientist at UHN. Her research explores cardiac tissue engineering and regenerative medicine, focusing on developing new biological materials and lab-grown heart tissue to treat heart failure and improve recovery after heart attacks.
For a full list of the 2025 CAHS Fellows, read the press release here.
Research conducted at UHN's research institutes spans the full spectrum of diseases and disciplines, including cancer, cardiovascular sciences, transplantation, neural and sensory sciences, musculoskeletal health, rehabilitation sciences, and community and population health.
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