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Unraveling the circuitry behind brain cancer

Collaborative research group identifies new cancer-driving mechanisms in brain cancer stem cells, describes novel ways to overcome the limited effectiveness of standard therapy

Dr. Graham MacLeod works at a lab bench at the University of Toronto.

Glioblastoma is the most common and the most deadly type of brain cancer found in adults, yet there have been no new advances in treating this disease for almost two decades. Recent research has provided a wealth of knowledge about the genomics – or the abnormal genetic code – of glioblastoma, but this has yet to translate into new treatments for patients. Understanding which genes drive glioblastoma can help uncover new ways to treat this incurable disease, and a pan-Canadian research group has set out to do just that.

Researchers from the University of Toronto, The Hospital for Sick Children and the University of Calgary have teamed up to identify genetic vulnerabilities in brain cancer stem cells – the cells that often resist treatment and cause the disease to return in patients after treatment. Their recent findings, which were published today in Cell Reports, uncovered new targets for glioblastoma and unraveled some of the complex mechanisms behind the disease.

Dr. Graham MacLeod

“We set out to understand which genes are important functionally,” says Dr. Graham MacLeod, co-primary author of the study and Research Associate in the lab of Dr. Stéphane Angers at the University of Toronto. “Connecting a gene to its function is a bit like connecting circuits on a very complex circuit board. If we can understand which genes are important, then we can find hints into where to unplug, plug in, stop and start mechanisms so that we can potentially stop the progression of the disease.”

The group used CRISPR-Cas9 gene editing tools, which Angers and MacLeod specialize in, to investigate all 20,000 genes within the genome and identify the key genes that are required for glioblastoma cells to survive and grow. In their study, they identified one gene in particular whose function is already targeted in leukemia treatments. Angers says this is promising “because it uncovered a biological process, not previously suspected to be implicated in glioblastoma, for which a small molecule drug already exists.”

As part of OICR’s Brain Cancer Translational Research Initiative, the next stage of their research will use the same gene editing approach to investigate tumour cells after therapy to find the genes or the genomic changes that help tumour cells evade treatment and recur in patients.

Read more about this research on University of Toronto News or learn more about the Stand Up To Cancer Canada Cancer Stem Cell Dream Team.

Researchers work to save lives by improving follow-up of colorectal cancer screening tests

Research group identifies the nuanced barriers that prevent patients from following up on a positive colorectal cancer screening test

Colorectal cancer (CRC) is often detectable and beatable, yet it still remains the second leading cause of cancer-related death in Canada. Ontario offers an at-home CRC screening test, however not all patients who have abnormal test results receive the necessary follow-up care due to a number of factors. This means that there are missed opportunities to treat – and cure – some of these cancers.

Dr. Jill Tinmouth at the Sunnybrook Research Institute has set out to improve follow-up after a positive CRC screening test. The first step, Tinmouth says, is to understand why patients may be reluctant to follow up in the first place.

Dr. Jill Tinmouth

“The screening test for colorectal cancer is an easy, safe, painless, at-home fecal occult blood test (FOBT) but without proper follow-up of abnormal tests, it is all for naught,” says Tinmouth. The FOBT checks a person’s stool for tiny drops of blood, which can be caused by CRC. Colonoscopy is the recommended next step for anyone who has an abnormal FOBT. “Looking at the administrative data, we saw that nearly one in three people with an abnormal FOBT don’t follow up with colonoscopy within six months. We are working to both understand and fix this gap.”

In this first study, Tinmouth and collaborators looked into Ontario’s administrative health data to try to improve the lack of follow-up. These initial findings suggested that physicians may not be adhering to screening guidelines and led to better articulation of CRC screening and follow-up protocols to primary care providers.

“We made some modifications to our screening program to encourage physicians to follow up on positive FOBT results in a timely manner, but we recognized that these strategies wouldn’t solve every problem,” says Tinmouth. “To fully understand the gaps and barriers to following up, we knew we had to speak directly to patients and those in this position.”

In their most recent study on the subject, published in the American Journal of Gastroenterology, Tinmouth teamed up with Dr. Diego Llovet from Cancer Care Ontario to interview patients who failed to follow-up on positive FOBT results and physicians who care for those patients. Many of the patients believed that their test results were a false positive and others experienced fear, anxiety or uneasiness about the next step in CRC screening – a colonoscopy. Often, patients were reluctant to have a colonoscopy and physicians were unable to persuade their patients to follow through.

Tinmouth is now working with health system decision-makers and Cancer Care Ontario to test and pilot four different interventions that could help improve proper follow-up, including patient navigation through the screening process and reminders sent to physicians of patients who test positive but fail to follow up. This research group is evaluating the feasibility of these interventions and how Ontario could implement them across the province.

“Better colon cancer screening and care starts with understanding the barriers and then effectively implementing this new knowledge,” says Tinmouth. “On these projects, researchers worked hand-in-hand with policy-makers – in so doing, we were able to integrate our expertise and collective wisdom to improve colorectal cancer screening for Ontarians today and in the future.”

The winner of last year’s FACIT Falcons’ Fortunes pitch competition is already seeing early success in moving her product to the clinic

The winner will soon meet with U.S. regulators, marking a major step towards commercializing her innovative polymer product, ReFilx™, and bringing it to breast cancer patients.

Dr. David O’Neill, President, FACIT, and Dr. Soror Sharifpoor, Co-Founder and Chief Executive Officer, Polumiros Inc., pose for a photo.

It took only 10 minutes for a panel of investors and industry experts to recognize that Dr. Soror Sharifpoor and her oncology product – ReFilx™ – were worth supporting. Last spring, she pitched ReFilx™ in the FACIT Falcons’ Fortunes competition and won the top prize – the $50,000 Ernsting Entrepreneurship Award. Almost 12 months later, Sharifpoor and her team at Polumiros Inc. will be meeting with the U.S. Food and Drug Administration (FDA) to officially begin the regulatory submission process – a necessary first step in bringing their product to patients.

ReFilx™ is a polymer designed to fill the breast tissue cavities left in breast cancer patients following a lumpectomy. The polymer dissolves over time, allowing the patient’s cells and tissue to regrow in its space, thus preventing breast tissue defects from forming.

“ReFilx™ could improve the emotional and mental well-being of breast cancer patients,” says Sharifpoor. “In addition to the psychosocial benefits, it could also encourage surgeons to take more aggressive margins around the tumour, thereby reducing the chances of cancer recurrence.”

Bringing ReFilx™ to the clinic requires rigorous clinical testing and regulatory review, which begins with a pre-submission meeting with the FDA. FACIT’s support allowed Sharifpoor to continue with pre-clinical testing, hire a regulatory consultant and further develop ReFilx™ into an injectable form.

In a few months, Sharifpoor and her team will have the pre-submission meeting to collect feedback on their product, which will then be used to guide their future submission to the FDA and their plans for further clinical research. Polumiros Inc. intends to pursue this research in Canada.

“We’re excited to initiate our regulatory submission process,” says Sharifpoor. “We’re fortunate to have had FACIT’s support, allowing us to develop ReFilx™ faster and smarter than we would have on our own.”

FACIT, OICR’s strategic partner in commercialization, is hosting its 6th annual pitch competition this year on April 4, 2019. The Falcons’ Fortunes event will feature six aspiring entrepreneurs from across the province who are developing oncology-related innovations. FACIT runs the annual competition as part of its broader mandate to support translation of cancer research to benefit Ontario’s economy and patients worldwide.

Learn more about Falcons’ Fortunes – FACIT’s annual pitch competition or read about this year’s event details.

Deep freezing allows researchers to dig deep into tumour samples

The Ontario Tumour Bank evaluates the quality of tumour samples stored at ultra-low temperatures over the last decade

Before they are used in cancer research, tumour samples are often preserved in storage at extremely low temperatures, sometimes for several years. It is thought that these temperatures can stop all biological activity in samples and thus prevent DNA, RNA and other analytes from degrading, but this technique has never been tested for extended long-term preservation – or storage beyond a few years. Researchers at the Ontario Tumour Bank (OTB) recognized this concern and looked back over a decade of specimens to find out more.

In their recent study published in Biopreservation and Biobanking, they investigated how the quality of a sample may change over the course of 10 years in vapour-phase liquid nitrogen storage, also known as LN2 storage. They found evidence to show that LN2 storage preserves the quality of genetic material in tumour samples over several years and no connection between the age of a sample and its integrity – or how intact its genetic material is.

“Our unique study has provided us, and the greater research community, with reassuring results,” says Rachel Kelly, Research Technician at OTB and lead author of the study. “While the biobanking community generally accepts that samples stored at ultra-low temperatures are stable indefinitely, we were concerned that this assumption had not been thoroughly tested.”

Kelly’s findings apply to the hundreds of biobanks around the world that store samples at cryogenic temperatures, or temperatures below -150⁰C. This study validates that researchers will be able to analyze and investigate well-preserved tissues, whether they are two years old or 10 years old.

“For the thousands of patients who have donated their samples, they should know that their contribution may impact cancer research for years to come,” says Monique Albert, Director of OTB. “At OTB, we have the privilege of diligently preserving this resource and helping translate valuable patient samples into new research discoveries.”

OTB, which stores more than 185,000 samples donated by over 20,000 patients across Ontario, is one of six founding Charter Member Banks of the Canadian Tissue Repository Network (CTRNet). Through CTRNet, these six top-tier biobanks work to enhance the capacity and quality of biobanking across Canada. Read more about how OTB is collaborating to improve biobanking around the world, or visit their website at ontariotumourbank.ca.

Europe and Canada build secure and efficient network to share genomic and health data

Dr. Lincoln Stein, Head, Adaptive Oncology, OICR.
Dr. Lincoln Stein, Head, Adaptive Oncology, OICR.

The Global Alliance for Genomics and Health introduces the European-CANadian Cancer network as one of seven new global Driver Projects

The rapid realization of precision medicine in oncology depends on the cancer research community’s ability to collaborate effectively. For genomics researchers, this means having the necessary computational tools and infrastructure to generate and share data.

Now, a new international initiative called The European-CANadian Cancer network (EUCANCan) has set out to align infrastructure across continents for the efficient analysis, management and sharing of cancer genomic and clinical data. On February 4, The Global Alliance for Genomics and Health (GA4GH) announced that EUCANCan has been named one of seven new GA4GH Driver Projects. 

“Our goal is to enable clinicians and researchers to exchange cancer data in a way that promotes effective analysis of this data while protecting patient privacy,” says Dr. Lincoln Stein, Head of Adaptive Oncology at OICR and leader of EUCANCan’s Toronto node. “With this network, we will be able to accelerate cancer genomics research on a global scale, and in turn, drive cancer discoveries that will lead to improved diagnostics and therapies.”

EUCANCan will realize its mission by uniting groups from Germany, the Netherlands, France, Spain and Canada into a federated network. The network will help define community standards for data formats, harmonize methods to interpret genomic data, and generate strategies to manage, store and distribute data across national borders.

As one of GA4GH’s new Driver Projects, EUCANCan aims to enrich collaborations between Canadian and European genomics groups while serving the greater global research community. The Toronto node, based at OICR, will be leading the development of an open and accessible data portal to allow the research community to search, download, and analyze EUCANCan data locally and in the compute cloud.

“Together, the new Driver Projects significantly expand GA4GH’s global representation, strengthening our collaborations across Africa and Europe, as well as in Japan, and adding connections in 31 countries for a total global reach across more than 100 countries worldwide,” says GA4GH CEO Peter Goodhand.

 “The new Driver Projects join a community that is building the standards and frameworks that will guide the field for years to come,” says Dr. David Altshuler, Founding Chair of GA4GH.

Read more about the 2019 Driver Projects here.

OICR supports cancer drug discovery in Ontario with new funding for four promising early-stage projects

Toronto (February 21, 2019 | Updated July 15, 2019) – The Ontario Institute for Cancer Research (OICR) today announced that three Early Accelerator projects from across Ontario will each receive $100,000 for one year as part of OICR’s Cancer Therapeutics Innovation Pipeline (CTIP) initiative. The funding will be used to validate cancer targets and support experiments to screen molecules against these targets, finding those that can bind to them successfully and have potential to be developed into medicines.

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Sometimes the simpler, the better: bringing personalized treatment selection for bladder cancer closer to the clinic 

Pathology slides sit in a tray on a lab bench top.

Pathology experts review challenges and opportunities in treatment selection for muscle-invasive bladder cancer (MIBC), propose traditional pathology method to achieve same results as molecular profiling at lower cost

Research has shown that some types of bladder cancer respond well to treatment and other types are resistant, yet molecular subtyping, which can help better define a patient’s cancer and direct them to a more targeted treatment, is not performed in the clinic. This means that patients are often treated with a one-size-fits-all approach. Despite recent research progress, the movement of MIBC subtyping to the clinic has stagnated.

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The power of one, benefiting the many

Close up of a person using a laptop.

When the first volunteer signed up for the Ontario Health Study (OHS), carefully filling out a detailed online health questionnaire, they no doubt hoped their efforts would do some good. They could never have predicted that, 10 years on, their de-identified health data is now pooled with those of nine million other altruists, from across four continents, in addition to being part of a Canadian national database.

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Dockstore: Sharing tools for large-scale genomics research

Denis Yuen, Senior Software Developer at OICR

OICR’s Adaptive Oncology team has been granted $875,000 from Genome Canada to expand Dockstore – a framework for generating and sharing portable computational biology workflows.

Cancer genomics research depends on the ability to analyze massive datasets in a standardized and coordinated manner. This involves creating and managing workflows – a series of processes and computational tools – that are often long, complex and difficult to share between research groups.

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FACIT and Triphase Accelerator Announce New Partnership with Celgene for First-in-class WDR5 Leukemia Therapy

Largest transaction to date for Canadian-discovered preclinical asset arises from Ontario collaborators 

TORONTO, ON (January 29, 2019) – Triphase Accelerator, together with its majority shareholder FACIT, today announced a new strategic collaboration with Celgene for a first-in-class preclinical therapeutic targeting the WDR5 protein for the treatment of blood cancers including leukemia. Triphase is a drug development company advancing novel compounds through Phase 2 proof-of-concept, including the WDR5 program. 

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