July 27, 2020

Evolving treatment to evolving tumours: How OICR-supported researchers are getting ahead of ovarian cancer

OICR-supported Phase II trial uncovers how ovarian cancers become resistant to treatment, identifies new opportunities to personalize treatment for future patients

Clinician investigator Dr. Stephanie Lheureux has seen many women fight ovarian cancer – some who overcome the disease and unfortunately many who die. These women inspire Lheureux to find new effective treatments and to continue improving how we treat the disease.

One remarkable patient inspired the EVOLVE trial. After years of keeping her ovarian cancer in check, her cancer began to grow again, indicating that it had become resistant to the maintenance treatment she was on. Lheureux presented the option of palliative chemotherapy, as the latest guidelines suggest, but her patient declined – she wanted a different treatment that would allow her to have a healthy life outside of the hospital.

Dr. Stephanie Lheureux

“This type of chemotherapy requires several visits to the hospital and it’s associated with side effects on patients’ hair, skin and nails,” says Lheureux, Clinician Investigator at the University Health Network’s Princess Margaret Cancer Centre. “This patient didn’t want to go on standard chemotherapy. She had participated in several clinical trials before, and she urged me to find her another option.”

Continue reading – Evolving treatment to evolving tumours: How OICR-supported researchers are getting ahead of ovarian cancer

June 29, 2020

New radiotherapy method improves long-term survival

OICR Investigator-led phase II clinical trial shows long-term advantage of ablative therapy for patients with multiple tumours. Technology enters phase III clinical testing.

Varian TruBeam®
© 2010 Varian Medical Systems International AG, All Rights Reserved

For a long time, if a cancer had spread to another part of a patient’s body, it was thought to be incurable. Dr. David Palma and collaborators are challenging this notion.

In the phase II SABR-COMET clinical trial, Palma and colleagues evaluated the long-term effects of a modern type of radiotherapy, called stereotactic ablative radiotherapy (SABR), on individuals with cancers that have spread to a few organs. The results from the trial, which were recently published in the Journal of Clinical Oncology, show that SABR can extend the lives of these patients by a median of 22 months with an improvement in five-year survival of 25 per cent.

Continue reading – New radiotherapy method improves long-term survival

June 23, 2020

Diagnosing brain tumours with a blood test

A blood test to diagnose and classify tumours could be revolutionary and practice-changing for patients and clinicians alike. In many cases, a simple blood sample could take the place of more invasive surgery to obtain tissue samples – resulting in better treatment planning and less anxiety for patients.

University Health Network’s (UHN) Drs. Daniel De Carvalho and Gelareh Zadeh collaborated to combine advanced technology with machine learning to develop a highly sensitive and accurate blood test to detect and classify brain cancers. Photo Credit: UHN

In an OICR-supported study recently published in Nature Medicine, researchers have shown that a simple but sensitive blood test can accurately diagnose and classify different types of brain tumours. With further research and development, the test could serve as a less-invasive method to detect, diagnose and classify the severity of brain tumours.

The study was also presented virtually on June 22 at the Opening Plenary Session of the American Association for Cancer Research Annual Meeting 2020: Turning Science into Lifesaving Care.

Continue reading – Diagnosing brain tumours with a blood test

June 11, 2020

Community-driven initiative finds new potential avenue of ovarian cancer treatment

Dr. Trevor Shepherd

OICR-funded researchers identify promising targets to shut down the spread of ovarian cancer

Despite new targeted therapies, ovarian cancers often spread to other organs in the body and become resistant to drugs, leading to nearly 2,000 deaths in Canada each year according to the Canadian Cancer Society. Dr. Trevor Shepherd is committed to finding new solutions for women with this disease.

In an initiative supported by local ovarian cancer survivors and philanthropic donors, Shepherd and collaborators have discovered a new way to shut down the spread of ovarian cancer. In their recent study published in Cancers, they found a molecular pathway that ovarian tumours require to spread to other organs. The study pinpoints two key proteins along this pathway – LKB1 and NUAK1 – as potential drug targets.

Continue reading – Community-driven initiative finds new potential avenue of ovarian cancer treatment

February 25, 2020

Study shows common cell protein could be targeted to treat childhood brain cancers

Researchers discover that childhood brain cancer could be treated by blocking key cell-surface protein, pointing to a potential treatment approach with fewer toxic side effects

Michelle Francisco, first author, and Dr. Xi Huang, senior author

Chemotherapy for children with brain cancer is often toxic, leaving patients with serious life-long side effects but OICR-funded researchers have uncovered a new approach that may help.

In a study published in the Journal of Experimental Medicine, the Ontario-based research team discovered that blocking a specific protein on the surface of brain cancer cells can suppress the rampant growth of a tumour without harming the development of the brain.

The study focused on the protein CLIC1 in medulloblastoma, the most common type of childhood brain cancer. The group found that disrupting CLIC1 can halt medulloblastoma growth with very little effect on the developing brain in mice.

“Brain cancer is the leading cause of cancer-related death in children and young adults,” says Dr. Xi Huang, Scientist in the Developmental & Stem Cell Biology Program at The Hospital for Sick Children (SickKids) and senior author of the study. “We need new treatments to help these patients.”

We believe our findings are significant because ion channels have been successfully targeted to treat numerous human diseases.

Michelle Francisco

CLIC1 belongs to a class of proteins called ion channels, which are important in the development of several other diseases like diabetes, epilepsy and high blood pressure. Many existing drugs and compounds act as ion channel modulators. The Huang Lab now has the high-throughput screening equipment to assess thousands of drug-like chemicals for those that can best block these ion channels.

“We believe our findings are significant because ion channels have been successfully targeted to treat numerous human diseases,” says Michelle Francisco, Research Project Coordinator in the Developmental & Stem Cell Biology Program at SickKids and first author of the study. “This helps pave the way between this discovery today and the impact it can have in the clinic.”

These findings build on Huang’s previous research on the potassium channel EAG2, which – like CLIC1 – is critical to medulloblastoma growth. In partnership with collaborators, Huang has shown that EAG2 could be blocked with an FDA-approved drug for schizophrenia to treat medulloblastoma in experimental mouse models and in a small patient study.

“We are fortunate to work with world-leading brain cancer researchers in Ontario,” Huang says, “We look forward to continuing our research to find new solutions for this devastating disease by targeting ion channels.”

This research was funded by OICR’s Brain Cancer Translational Research Initiative, SickKids Foundation, Arthur and Sonia Labatt Brain Tumour Research Centre, Garron Family Cancer Centre, b.r.a.i.n.child, Meagan’s Walk, Natural Sciences and Engineering Research Council (NSERC) Discovery Grant, U.S. Department of Defense (DoD) Peer Reviewed Cancer Research Program Career Development Award, Canadian Institute of Health Research (CIHR) Project Grants, and Sontag Foundation Distinguished Scientist Award to Xi Huang.

Read more about OICR’s brain cancer research.

February 5, 2020

AI algorithm classifies cancer types better than experts

Gurnit Atwal and Wei Jiao

Pan-Cancer Project researchers develop deep learning system that can determine where a cancer originates with better accuracy than human experts

If doctors know where a patient’s cancer started, they can better treat the disease. Unfortunately, this is not always possible, but AI could play a role in solving that.

In a study published today in Nature Communications, a Toronto-based researcher group developed a deep learning system that can accurately classify cancers and identify where they originated based on patterns in their DNA. The system could potentially help clinicians differentiate difficult-to-classify tumours and help recommend the most appropriate treatment option for their patients.

“We reasoned that there was something within the cancer’s DNA that could help us classify these tumours,” says Dr. Quaid Morris, OICR Senior Investigator and co-lead author of the study1. “But I didn’t expect our system to work at well as it does – in some cases, far better than pathologists.”

The team

The initiative began with the dataset: 2,600 whole genomes across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes Project, also known as the Pan-Cancer Project or PCAWG.

Dr. Lincoln Stein, Head, Adaptive Oncology at OICR and member of the Pan-Cancer Project Steering Committee, and his team began to work with these data to identify patterns in a cancer’s genetic material that could help classify these tumours. To them, this was a perfect problem for AI.

When we started to collaborate, We realized we had something amazing.
– Wei Jiao

“Deep learning models excel when they’re trained on large amounts of data,” says Wei Jiao, Research Associate in the Stein Lab and co-first author of the study. “We had an incredibly large dataset to work with, the most comprehensive dataset of whole cancer genomes to date, but we also needed the machine learning expertise.”

The Stein Lab posted their progress on bioRxiv, an open-access repository for biology publications that have not yet been peer-reviewed, which in turn sparked the collaboration between his team and the Morris Lab – a group with deep machine learning expertise.

The system

The development of their deep learning system was not simple. They mined through terabytes of data looking for patterns in the type of mutations, the source of mutations and where mutations occurred in the genome, among other factors.

To their surprise, they found that patterns in driver mutations – the changes in DNA that are thought to ‘drive’ the development of cancer – were not useful in determining where the tumour originated. Instead, they found that patterns in the distribution of mutations and the type of mutation within a patient’s sample could better classify the patient’s disease.

“We knew that we could distinguish between two different types of healthy cells by looking at how the DNA within the cell types are packaged,” says Stein, who is a co-lead author of the study. “We were surprised and gratified that we could do the same using cancer cells.”

“We saw that the tightly-packaged sections – also known as the closed chromatin – would have many more mutations than the loosely wound sections,” says Gurnit Atwal, PhD Candidate in the Morris Lab and co-first author of the study. “It was like the normal cell was casting a shadow on the cancer cell, and we just had to read the shadows.”

To achieve the highest accuracy, the research group developed a deep learning neural network-based system, a type of system that is loosely modeled after the human brain and commonly used to recognize patterns in images, audio and text. Their system achieved an accuracy of 91 per cent – roughly double the accuracy that trained pathologists can achieve using traditional methods when presented with a primary tumour and no clinical information.

Further, they tested their model on an additional 2,000 tumours from patients in the Netherlands who donated their cancer genomic data to the Hartwig Medical Foundation and the system still performed with a remarkably high level of accuracy.

 “As more cancer genomes are sequenced, we can gain the ability to classify rarer cancers,” says Atwal. “Where we are now is great, but there is more work to be done.”

The potential

This study presents a deep learning system that could potentially improve how cancers are classified, enhancing the accuracy of current diagnostic tests and the treatment decisions they inform.

For some patients, this system could tell them where their cancer began, giving them valuable information about which course of treatment to choose. The system also could serve as a tool to help doctors identify whether a tumour in a patient who has been treated for cancer in the past is an entirely new tumour or a recurring tumour that has spread.

“A treatment plan for a cancer that originated in the throat may be very different than one for that originated in the breast, and the treatment for a cancer that has returned is different than for one that has metastasized,” says Atwal. “One day, our tool could help give doctors the power to distinguish these classes of tumours, giving patients valuable information that wouldn’t have been available otherwise.”

The authors of the study suggest that their system could start helping patients soon. They plan to further refine their system for patients with rare cancers before moving towards clinical studies. 

“The potential impact of the system we’ve developed is encouraging,” says Morris. “We look forward to turning this system into a tool that can help clinicians and future cancer patients tackle this disease.”


1Morris is also a Canada CIFAR AI Chair, Faculty Member at the Vector Institute, and Professor at the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research.


Related links

January 13, 2020

Unique Toronto-based clinical trial reveals new subtypes of advanced pancreatic cancer

Drs. Faiyaz Notta and Steven Gallinger, Co-Leaders of OICR’s Pancreatic Cancer Translational Research Initiative (PanCuRx).

Researchers identify five subtypes of pancreatic cancer, uncovering new opportunities for targeted treatment of the aggressive disease

Toronto – (January 13, 2020) Researchers at the Ontario Institute for Cancer Research (OICR) and the University Health Network (UHN) have discovered detailed new information about the subtypes of pancreatic cancer. A better understanding of the disease groups may lead to new treatment options and improved clinical outcomes for this lethal disease.

The study, published today in Nature Genetics, represents the most comprehensive analysis of the molecular subtypes of pancreatic cancer to date. Through detailed genomic and transcriptomic analyses, the research group identified five distinct subtypes of the disease (Basal-like-A, Basal-like-B, Classical-A, Classical-B, and Hybrid) with unique molecular properties that could be targeted with novel chemotherapies, biologics and immunotherapies.

“Therapy development for pancreatic cancer has been hindered by an incomplete knowledge of the molecular subtypes of this deadly disease,” says lead author Dr. Faiyaz Notta, Co-Leader of OICR’s Pancreatic Cancer Translational Research Initiative (PanCuRx) and Scientist at UHN’s Princess Margaret Cancer Centre. “By rigorously analyzing advanced pancreatic cancers – which is the stage of disease that most patients have when they’re diagnosed – we were able to create a framework. This will help us develop better predictive models of disease progression that can assist in personalizing treatment decisions and lead to new targeted therapies.”

The study is based on data from more than 300 patients with both early stage and advanced pancreatic cancer who participated in COMPASS, a first-of-its-kind clinical trial that is breaking new ground in discovery science and personalized pancreatic cancer treatment. COMPASS is enabled by advanced pathology laboratory techniques at UHN and OICR, and next generation sequencing at OICR.

“Most pancreatic cancer research is focused solely on early stage – or resectable – tumours, but in reality, pancreatic cancer is often found in patients after it has advanced and spread to other organs,” says Notta. “COMPASS allowed us to look into these advanced cancers while treating these patients, develop a better understanding of the biology behind metastatic pancreatic cancer, and shed light on the mechanisms driving disease progression.”

Interestingly, the Basal-like-A subtype, which had been difficult to observe before this study, was linked with a specific genetic abnormality. Most of the Basal-like-A tumours harboured several copies of a mutated KRAS gene, also known as a genetic amplification of mutant KRAS. The research group hypothesizes that some of the subtypes arise from specific genetic changes that occur as pancreatic cancer develops.

“This research opens new doors for therapeutic development,” says Dr. Steven Gallinger, Co-Leader of OICR’s PanCuRx, Surgical Oncologist at UHN and Senior Investigator, Lunenfeld Tanenbaum Research Institute at Mount Sinai Hospital. “We look forward to capitalizing on the promise of these discoveries, building on our understanding of pancreatic cancer subtypes, and bringing new treatments to patients with the disease.”

This research was supported by OICR through funding provided by the Government of Ontario, and by the Wallace McCain Centre for Pancreatic Cancer by the Princess Margaret Cancer Foundation, the Terry Fox Research Institute, the Canadian Cancer Society Research Institute, the Pancreatic Cancer Canada Foundation, the Canadian Friends of the Hebrew University and the Cancer Research Society (no. 23383).

November 18, 2019

Potential new approach to T-cell therapy shows early promise in the lab

Drs. Yonghong Wan and Scott Walsh
Drs. Yonghong Wan and Scott Walsh

McMaster University researchers validate a new treatment approach that could help bring the benefits of Adoptive T-cell therapies to patients with solid tumours

Adoptive T-cell therapy (ACT) is an emerging form of immunotherapy that uses a patient’s own re-engineered immune cells to eliminate their cancer. Although ACT is effective against specific types of cancer, like certain blood cancers, these therapies are ineffective against the majority of common tumours.

Researchers at McMaster University are developing a new combination approach that could overcome the limitations of current ACT, and bring the benefits of this promising therapy to many more patients.

The approach, as recently described in The Journal of Clinical Investigation, combines ACT with specially-designed vaccines, called oncolytic virus vaccines (OVVs), to bring about the complete destruction of a solid tumour.

Dr. Scott Walsh, Postdoctoral Fellow in Dr. Yonghong Wan’s lab at McMaster University and first author of the publication, describes the “push and pull” mechanism behind their combination approach.

“We found that oncolytic viruses could stimulate the implanted T-cells to proliferate. In other words, they could push the cancer-fighting cells to multiply,” says Walsh. “Then we found that these viruses could also pull the cancer-fighting T-cells into the core of the tumour, which simply could not be done with ACT alone.”

In this study, the research group discovered that their ACT/OVV combination approach could engage the entire immune system to eliminate solid tumours and generate a long-term tumour-resisting effect in experimental animal models. Whereas current ACT can only kill specific tumour cells, their approach was effective at eliminating the various types of cells within solid tumours.

“Usually, ACT can only target the tumour cells that have a specific set of molecular markers. This is a problem because tumours can often shed these marked cells and return with a vengeance,” Walsh says. “Our approach engages the immune system as a whole, not just the re-engineered cells, to eliminate a broader variety of tumour cells and prevent the tumour from coming back over the long term.”

To bring this new approach into the next stage of development, the study group teamed up with experts across the province through OICR’s Immuno-oncology Translational Research Initiative. The team includes researchers with deep immuno-oncology expertise and extensive commercialization experience.

“Bringing this idea into the next stage of development requires collaboration across areas of expertise,” says Walsh, who holds a patent on the combination approach. “We’re looking forward to building on our past successes and using our collective expertise to move into more advanced animal models, and then onto clinical trials.”

October 15, 2019

‘I’m here to help address important and challenging questions in health’

OICR Biostatistics Training Initiative Fellow and newly-minted PhD, Dr. Osvaldo Espin-Garcia, dedicates his career to cutting-edge clinical cancer research

Osvaldo Espin-Garcia

For Dr. Osvaldo Espin-Garcia, an industry-based job wouldn’t suffice. Having already worked in banking, insurance and telecommunications, Espin-Garcia found that his skills in statistics could be applied to a field that he was much more passionate about. For him, that was health research.

Combining his skills in math with his interest in health, Espin-Garcia left his job in Mexico and moved to Canada to pursue the University of Waterloo’s Master of Mathematics program. His strong academic performance secured him an internship at the Princess Margaret Cancer Centre (PM) where he found his niche in statistical genetics.

“Despite advancements in sequencing technologies, the path between a new -omics discovery and applying that discovery in the clinic remains cumbersome and often costly, especially in large-scale studies,” says Espin-Garcia, who recently completed his PhD at the University of Toronto’s Dalla Lana School of Public Health. “We can use statistical techniques and tools to design better trials and make sense of this sequencing data in more efficient ways.”

Espin-Garcia’s internship laid the foundations for his PhD research, where he developed statistical methods and analysis tools to examine the data from genome-wide studies – studies that look at the entire set of genes across many individuals.

In these studies, researchers often examine a sample subset of patient genomes from a large group of patients. These samples are often selected randomly, but Espin-Garcia’s methods allow researchers to select these patients in a “smarter” way.

“Choosing patients randomly is an inefficient way to perform post-genome-wide studies since this strategy fails to incorporate the information that is already available,” says Espin-Garcia. “Our methods allow us to select subgroups of patients whose data will give us rich insights into challenging research questions. That’s what I’m here for, I’m here to help address important and challenging questions in health.”

For this work, Espin-Garcia was awarded a Biostatistics Training Initiative (BTI) Fellowship, which helped him fast-track the development of his methods and the completion of his PhD.

Now, as a Senior Biostatistician at PM, he is specializing in gastrointestinal cancer studies and continues to develop and apply new tools to support the clinical cancer research community.

“I am grateful for the support I’ve received throughout my training to build my collaborative relationships with clinicians and scientists and learn from incredible mentors,” says Espin-Garcia. “I look forward to supporting more cutting-edge clinical cancer research in the future.”

BTI, a training program co-led by OICR, the University of Waterloo and McMaster University, has supported numerous fellows, like Espin-Garcia, and other studentships over the last decade.

To learn more about the BTI Program, please visit the OICR BTI Program page, the University of Waterloo’s BTI webpage or read more about some of the past studentships.

September 20, 2019

Harnessing the time before a patient’s surgery to accelerate cancer research

Ottawa cancer researchers and clinicians embrace the window of opportunity between a cancer diagnosis and treatment with a coordinated approach to clinical research

The time between a patient’s cancer diagnosis and their surgery presents a valuable “window of opportunity” to evaluate new treatment strategies. Short-term clinical trials during this period – also known as window of opportunity trials, window trials or phase 0 trials – can help researchers gain insights into the effects and the efficacy of a new potential treatment. Dr. Angel Arnaout at The Ottawa Hospital is putting window trials into practice.

“There are many nervous and anxious moments between diagnosis and their surgery but patients have limited options during this time,” says Arnaout.

“We saw an opportunity in this window of time to take action. We saw that we could help support patients who are waiting for surgery, while helping future patients through accelerating clinical research.”

Dr. Angel Arnaout

Arnaout, a surgical oncologist who specializes in breast cancers, assembled a cross-disciplinary team of medical oncologists, pathologists and other clinical research specialists at The Ottawa Hospital to strategically design and implement this new approach. They would collectively establish common priorities, decide on which interventions would be tested and work to streamline the patient’s journey throughout the process.

Dr. Angel Arnaout

Together, the team was motivated by the mutual benefits of all stakeholders involved. Namely, window trials can provide patients an opportunity to contribute and engage with cancer research while potentially improving the state of a patient’s disease. Meanwhile, these trials could ultimately expedite drug development by improving the understanding of a potential drug early in its development.

The team launched their first study in 2014, which found that patients were exceptionally eager to participate, and since then, launched and completed three additional window trials.

The first was a breast cancer trial on presurgical hormone therapy that helped establish the capacity and infrastructure for enrolling patients, organizing the investigations and giving patients short-term therapies. The second tested a potential cancer-fighting agent, chloroquine, and found that it had no effect on stopping breast cancer proliferation. The third trial debunked the idea that vitamin D – even at very high doses – can slow down the growth of breast cancer.

“These studies didn’t uncover a new therapy, but they did help us answer important questions that patients have, like ‘Will taking vitamin D help?’” says Arnaout. “These types of studies also provide a relatively quick method to test whether we should continue research into a particular avenue.”

The group at The Ottawa Hospital has recently teamed up with researchers from OICR to initiate a new breast cancer window-of-opportunity study to examine biomarkers of efficacy and resistance for another new drug candidate. The trial is planned to begin recruitment by mid-fall this year.*

Despite the benefits of these trials, Arnaout adds, it is still important to reduce unnecessary delays between diagnosis and surgery. Arnaout continues to minimize these delays at The Ottawa Hospital.

“We try our best to reduce wait times, but if patients have to wait – we can try to help them in the meantime while accelerating breast cancer research.”

*This new trial is co-led by Dr. John Hilton from The Ottawa Hospital and Dr. John Bartlett from OICR. Co-investigators include Drs. Laszlo Radvanyi, Melanie Spears, Arif Ali Awan, Mark Clemons, Greg Pond and Angel Arnaout.

July 29, 2019

Computational dissection: What can we learn from the cells around cancer cells?

OICR researcher looks into what non-tumour cells can tell us about breast cancer

Natalie Fox
Natalie Fox, OICR

When a biopsy is drawn from a patient, it consists of a mix of cancerous and healthy cells, like fat and blood cells. Researchers are often interested in diseased cells, but without looking into the surrounding tissue, they could be missing part of the story.

Natalie Fox, a PhD candidate at OICR, is investigating what we can learn from the cells surrounding cancer cells.

“When we look into a patient sample computationally, we see distorted signals because of overlapping data from many different types of cells,” says Fox. “We need to dissect the parts we want to study, but instead of using a knife or a laser, we use computers.”

Fox and collaborators have analyzed nearly 1800 tumour samples from patients with breast cancer, examining the transcriptome of tumour cells and the cells around tumours – or the tumour’s microenvironment.

Her study, recently published in Nature Communications, reveals the landscape of transcriptomic interactions between breast cancers and their microenvironments. Her study also sheds light on associations between these transcriptomes and patient survival, gene mutations and breast cancer subtypes.

“We now have a clearer picture that tells us more about the breast microenvironment than we’ve known before,” Fox says. “Bit by bit, we’ve analyzed and scrutinized these data, then assembled these bits into a comprehensive landscape.”

Fox found that mutations in cancer genes such as CDH1 and TP53 are associated with changes in the transcriptome of the tumour’s microenvironment. She says more research is needed to clarify the biologic rationale behind her observations, but her work has set the stage for researchers to do so.

“Above all else, this work demonstrates an important approach for improving our understanding of associations between the tumour and the microenvironment,” Fox says. “We presented a framework that others can use to analyze the tumour microenvironment in their cancer of interest and potentially develop new biomarkers for predicting cancer patient outcomes.”

July 17, 2019

New research unfolds the DNA “origami” behind brain cancers

Collaborative research group maps the three-dimensional genomic structure of glioblastoma and discovers a new therapeutic strategy to eliminate cells at the roots of these brain tumours

Current treatment for glioblastoma – the most common type of malignant brain cancer in adults – is often palliative, but new research approaches have pointed to new promising therapeutic strategies.

A collaborative study, recently published in Genome Research, has mapped the three-dimensional configuration of the genome in glioblastoma and discovered a new way to target glioblastoma stem cells – the self-renewing cells that are thought to be the root cause of tumour recurrence.

The research group integrated three-dimensional genome maps of glioblastoma with other chromatin and transcriptional datasets to describe the mechanisms regulating gene expression and detail the mechanisms that are specific to glioblastoma stem cells. They are one of the first groups in the world to perform three-dimensional genomic analyses in patient-derived tumour samples.

Dr. Mathieu Lupien

“The 3D configuration of the genome has garnered much attention over the last decade as a complex, dynamic and crucial feature of gene regulation,” says Dr. Mathieu Lupien, Senior Scientist at the Princess Margaret Cancer Centre, OICR Investigator and co-author of the study. “Looking at how the genome is folded and sets contacts between regions tens to thousands of kilobases apart allowed us to find a new way to potentially tackle glioblastoma.”

Through their study, the group discovered that CD276 – a gene which is normally involved with repressing immune responses – has a very important role in maintaining stem-cell-like properties in glioblastoma stem cells. Further, they showed that targeting CD276 may be an effective new strategy to kill cancer stem cells in these tumours.

Lupien adds that advancements in three-dimensional genomics can only be made through collaborative efforts, like this initiative, which was enabled by OICR through Stand Up 2 Cancer Canada Cancer Stem Cell Dream Team, OICR’s Brain Cancer Translational Research Initiative and other funding initiatives.

“This research was fueled by an impressive community of scientists in the area who are committed to finding new solutions for patients with brain cancer,” Lupien says. “Our findings have emphasized the significance of three-dimensional architectures in genomic studies and the need to further develop related methodologies to make sense of this intricacies.”

Senior author of the study, Dr. Marco Gallo will continue to investigate CD276 as a potential therapeutic target for glioblastoma. He plans to further delineate the architecture of these cancer stem cells to identify more new strategies to tackle brain tumours.

Dr. Marco Gallo

“A key problem with current glioblastoma treatments is that they mostly kill proliferating cells, whereas we know that glioblastoma stem cells are slow-cycling, or dormant. Markers like CD276 can potentially be targeted with immunotherapy approaches, which could be an effective way of killing cancer stem cells, irrespective of how slowly they proliferate,” says Gallo, who is an Assistant Professor at the University of Calgary. “Being able to kill cancer stem cells in glioblastoma could have strong implications for our ability to prevent relapses.”

Read more about OICR’s Brain Cancer Translational Research Initiative on oicr.on.ca or read about the Initiative’s current findings on OICR News.

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