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Drug Discovery scientist wants to speed up development of new cancer therapeutics

Dr. Masoud Vedadi joined OICR in 2022, bringing a wealth of experience in characterizing targets for new cancer drugs.

OICR bolstered its capacity to develop new cancer therapeutics in 2022 with the addition of Dr. Masoud Vedadi, a world-renowned expert in early-stage drug discovery.

Vedadi is an Associate Professor in the University of Toronto’s Pharmacology and Toxicology Department who spent the last two decades as Principal Investigator for the Structural Genomics Consortium (SGC).

With expertise in enzymology, biochemistry and protein science, Vedadi regularly collaborated with OICR in his role with SGC and is one of the key scientists behind the groundbreaking WDR5 project. In July 2022, he officially joined OICR as Senior Scientific Advisor, bringing a wealth of experience to OICR’s expert team of Drug Discovery researchers.

OICR News recently spoke to Vedadi about his accomplished career and his aims for his new role.

Why did you get involved in drug discovery for cancer?

I have always been passionate about science, and my specific interests have largely been motivated by unmet needs in society. Cancer, of course, is such a major challenge all over the world. It causes so many people to suffer, and I want to help reduce that suffering by developing effective treatment options.

My passion to contribute has also led me in other directions based on world events. For example, during the coronavirus pandemic over the past few years, I have been contributing to projects to develop COVID-19 therapeutics and we have had successes on that front.

Tell us about your new role as Senior Scientific Advisor with OICR.

In early-stage drug discovery, we try to identify molecules that can influence the function of disease-causing proteins. In many cases, cancers are driven by a particular protein. If we can reduce the effect of the protein, we may be able to stop cancer from growing. At its core, my job is to find small molecules that modulate the function of disease-causing proteins so that they can be turned into anti-cancer drugs and give physicians a tool they can use against the disease.

What attracted you to OICR?

Working with a great team matters a lot to me, and I have always been impressed with Dr. Rima Al-Awar’s team at OICR. We collaborated extensively for several years while I was working with the SGC, and our teamwork paid off with some major advancements, including our discoveries around the WDR5 protein and other drug discovery projects. Throughout all our collaborations, the chemistry and biology teams at OICR were very knowledgeable and competent, and my positive experiences with them were part of why I chose to join OICR last year.

How will your experience working with industry benefit you in this role?

One of my first positions after completing my PhD in biochemistry was with Affinium Pharmaceuticals. I’ve also run projects in collaboration with major companies like Pfizer, Novartis, Bayer, Merck, Takeda and many others. This experience has given me an in-depth view of how to make drug discovery projects more successful from start to finish. I’ve learned about the challenges faced at each step and ways to overcome them.

What are your goals for Drug Discovery at OICR?

The time between finding a small molecule and the development of an anti-cancer drug can be quite long. But we can shorten that timeline if we can quickly find molecules to start with. The more reliable, potent, and selective molecules we have as starting points, the better chance that one will be effective in a clinical trial and be on the path to helping patients. Therefore, I want to give OICR’s Drug Discovery team access to as many proteins as possible, anytime they need them, so they can identify potential drug targets.

How are you working to achieve these goals so far?

Since starting my role in July 2022, I have been working to create three components to strengthen early-stage drug development at OICR: a platform for protein production, a platform for protein crystallization, and important screening assays. I’m excited to have brought in some highly qualified team members to help lead this work and we are making great strides. These developments will give OICR the ability to produce, screen, characterize and crystallize proteins, allowing the whole Drug Discovery team to work more efficiently and shorten the timeline for bringing successful drugs to the clinic.

The Next Generation: Ido Nofech-Mozes

OICR PhD candidate developed a computational tool to classify cells in the tumour microenvironment.

Ido Nofech-Mozes hopes the tool he created can help answer some important questions about cancer.

Nofech-Mozes is a University of Toronto PhD candidate based in Dr. Sagi Abelson and Dr. Philip Awadalla’s labs at OICR. He recently created scATOMIC, a computational method that uses data from single-cell RNA sequencing to classify the different cells in a tumour microenvironment.

For a given tumour, scATOMIC can identify the types of cancer cells, immune cells and other cells that are present. Nofech-Mozes hopes the tool can enable large-scale studies to better understand cancer at a cellular level, and bring about more personalized treatment for people with cancer.

“I’ve learned that every cancer patient can be thought of as having their own unique disease and having their own unique set of challenges,” he says. “The variation between cancer patients is really putting an emphasis on why we need a more personalized, precision approach to cancer therapy.”

New directors of OICR Diagnostic Development program set sights on bringing discoveries to the clinic

Dr. Jane Bayani and Dr. Melanie Spears are helping bring new diagnostic tools to patients in their roles as Co-Directors of OICR’s Diagnostic Development program.

After more than a decade at OICR driving innovations in cancer diagnostics, Dr. Jane Bayani and Dr. Melanie Spears are leading OICR’s Diagnostic Development program toward even greater clinical impact. The longtime collaborators were named Co-Directors of the program in September 2022 after a period as Interim Co-Directors.

Bayani and Spears are both leaders in the field of cancer diagnostics, having pioneered innovative research into biomarkers for breast cancer and prostate cancer. Spears started with OICR in 2011 after earning her PhD from the University of Edinburgh and doing postdoctoral fellowships at the university and at Cancer Research UK. Bayani joined OICR in 2012 with research experience at Princess Margaret Cancer Centre and the Hospital for Sick Children and a PhD from the University of Toronto. Both also serve as Principal Research Scientists at OICR and Assistant Professors in the University of Toronto’s Department of Laboratory Medicine and Pathobiology.

Bayani and Spears were previously Associate Directors of OICR Diagnostic Development, working with former Director Dr. John Bartlett until he stepped down in July 2021. They were named Interim Co-Directors of the program in August 2021.

As they enter their first full year as permanent Co-Directors, OICR News checked in with Bayani and Spears about their new positions and their vision for the future of the program.

What does this new role mean to you professionally?

MS: Becoming Co-Director alongside Jane feels like a natural progression to the next stage of my career. I’m excited to grow within the role both as an independent researcher and together with our program’s local and international collaborators.

JB: This leadership role is the beginning of a new period where I can build on a solid foundation from my academic and professional careers. It will allow me to expand my research interests and continue my longtime partnership with Melanie, knowing we share the same goals and will continue to support each other’s aspirations.

What attracted you to the role?

MS: Being part of OICR offers great opportunities to work with networks of researchers – both within the institute and across the province – who bring diverse perspectives and expertise to Diagnostic Development’s various projects.

JB: We really do have an amazing and diverse multidisciplinary team all working toward a common goal. We are also fortunate to have a lab with state-of-the-art platforms for discovering and validating new biomarkers for cancer.

What inspired your interest in new diagnostic tools for cancer?

JB: We’ve all been impacted by cancer in some way, and I’m proud to be helping advance discoveries that can help people with cancer. I also hope I can be a role model for other women in science, just as I have been inspired by many women scientists over the years.

MS: I’ve always been interested in bringing technologies from the lab into clinical settings, and this is an area where I know we can have a meaningful impact on patients by helping find cancer earlier, when they will have the best chance of surviving it.


What excites you about the future of Diagnostic Development at OICR?

JB: We are now exploring some exciting new avenues to derive biomarkers beyond DNA and RNA. We are even looking at integrating aspects of digital pathology with protein markers. Melanie and I also look forward continuing our work with FACIT to advance the diagnostic assays we developed over the past few years.

MS: I’m excited for some of the new technologies we’re working with, including a project where we are exploring the use of spatial biology to understand how different cells interact within a tumour and how this impacts patient outcome. Our group has also developed some interesting predictive and prognostic diagnostic tests, and I’m keen to see these implemented in the clinical setting.

Can tumours shrink with a placebo alone?

Dr. Bishal Gyawali investigated how often cancer shrinks without treatment by looking at results from the placebo arm of randomized control trials.

When Dr. Bishal Gyawali prescribes treatment to newly diagnosed cancer patients, he is sometimes confronted with a tough question: “Could my cancer go away even if I don’t do treatment?”

He says some of his patients are wary of the side effects of treatments like chemotherapy, and some know a friend or relative whose cancer improved without treatment. So, they wonder if treatment is absolutely necessary.

“These are reasonable questions, and I realized I had no evidence-based way to answer them,” says Gyawali, a Medical Oncologist and Associate Professor at Queen’s University and OICR Clinician Scientist. “So, I decided I should look into it.”

Dr. Bishal Gyawali

Gyawali and colleagues reviewed results from 45 placebo-controlled randomized control trials (RCT) for drugs targeting advanced solid tumours in adults. In these RCTs, participants were randomly split into two groups: a treatment arm that received the treatment being trialed, and a control arm that received a placebo. Though the use of placebos is rare in cancer clinical trials, comparing results from a group that receives a drug versus a group that doesn’t can help understand what effect that drug has.

Since participants in the control arm of the trials Gyawali and colleagues analyzed only received a placebo – without any other active treatments – the progress of their tumours during the trial gives a good indication of how cancer responds without treatment.

Here, Gyawali tells OICR news about the results of their study and what they mean for clinicians and drug regulators.

What did you learn about tumour response among patients in the placebo arm of randomized trials?

We found that about one per cent of patients had some response from placebo alone. So yes, there is a chance a tumour will shrink without treatment. It’s a very small chance against a high-stakes disease like cancer. But it is possible. Beyond that, we also looked at ‘complete response’, meaning that a tumour disappears completely. We found there was almost a zero per cent chance of that happening with just a placebo.

How do you explain that some patients had tumours shrink while on a placebo?

We don’t know for sure. It could be the ‘placebo effect’ or it could be something a patient did outside of the trial that somehow affected their tumour.

In some trials, we saw a surprisingly high response rate in the placebo arm. The rate was about seven per cent in prostate cancer trials, which might be because prostate cancer patients are often given steroids in addition to cancer drugs. Sarcoma trials also had high response rates in the placebo arm, which is intriguing because sarcoma is usually difficult to manage. But it’s important to note that complete response was extremely rare without treatment. A tumour disappearing is a nearly unthinkable result from a placebo.

What does this tell us about how we should evaluate new cancer treatments?

In a few of the trials we examined, we saw response rates as high as 20 per cent in the placebo arm, which is higher than the response rates used by regulators to approve some new therapies. That’s important for regulators because, if a placebo can produce response in a tumour, the response rate from a single-arm trial that tests new cancer drugs can be misleading. I would suggest that approvals for new therapies should be based on RCTs, because we need to know the response rate in the control arm to truly understand the impact of a new cancer drug. If approval is granted from a single-arm trial, then it should be based on complete response rates rather than overall response rates because we know that complete response is almost always due to the drug.

How will these findings change your conversations with patients about whether to do treatment?

This gives me data to respond to patients who may question the value of doing treatment. We can have an unbiased, scientific conversation without discounting their opinions or experiences. I can tell them yes, there is about a one per cent chance your tumour will shrink without treatment, and basically no chance it will completely disappear. Is that a chance you’re willing to take?

Zooming in on mouse brain development reveals origins of human glial cancers

OICR researchers create first-of-its kind atlas of developing mouse brain cells to help find the ‘cell of origin’ for brain and spinal cord tumours

By looking closely at the building blocks of normal brain development, researchers may have pinpointed where glial cancers start, and uncovered clues on how to stop them.

A study led by SickKids’ Dr. Peter Dirks, recently published in Nature Communications, explored the relationship between a primitive type of brain cell called radioglial precursors (RGPs) and the cells of glial tumours, which form in the brain and spinal cord.

Precursor cells are usually present before birth, and RGPs are involved in the early development of the brain. But researchers have observed that RGPs share common traits with certain glial cancer cells and have long suspected that glial cancers may originate from RGPs.

Dirks, PhD candidate Akram Hamed and other collaborators investigated by doing single cell transcriptomics on more than 100,000 brain cells from mice to create a detailed atlas of the developing mouse brain.

“We really zoomed in on precursor cells, which allowed us to see the richness of the diversity within these cells,” says Dirks, who is also Co-Leader of OICR’s Brain Cancer Translational Research Initiative.

From this first-of-its-kind atlas, they classified three types of RGP that had not been identified before: embryonic, juvenile and adult. Then they used an advanced algorithm to compare their mouse brain atlas to single-cell data from more than a hundred human glial cancers.

The comparison showed a significant connection between RGPs at the embryonic stage and certain glial cancer cells, suggesting that glial tumours do in fact arise from these primitive cells.

“Now that we think we’ve discovered the ‘cell of origin’ for glial cancers, we can study what causes that cell to veer off course and become cancer, and potentially develop therapeutics to persuade it to go back down its regular developmental pathway,” says Dr. Lincoln Stein, Head Adaptive Oncology, OICR and a collaborator on the study. Stein’s lab, including PhD candidate Ibrahim El-Hamamy, developed the algorithm that allowed for the mouse-human cell comparison.

Working with Stein and fellow collaborator Professor Benjamin Simons of the University of Cambridge, Dirks and colleagues went on to validate these findings by engineering mutations to embryonic cells in developing mouse brains. Sure enough, the mice went on to develop tumours in adulthood that resembled glioblastoma.

Work on this study continues, with plenty left to learn about the relationship between embryonic precursor cells and brain tumours. There are still competing hypotheses about whether the study’s findings mean that glial cancers originate before we are born, or whether something happens later in life to cause mature cells to ‘walk back’ developmentally to embryonic states.

Dirks and colleagues hope to provide more answers as their research progresses. But what they have learned so far about the types of precursor cells and their relationship with cancer could have major implications for stopping glial cancers in the future.

“When cancers like glioblastoma present, they are so complex that they can often evade our therapies,” Dirks says. “If we understand the mechanisms in normal cells that make them transition to cancer, we might be able to identify patients earlier and stamp out the cancer before it gets too complicated.”

‘Seemingly inconsequential’ inherited DNA mutation triggers sixfold increase in brain tumour risk

Dr. Daniel Schramek never expected to find a major driver for brain tumours in a hidden corner of our DNA.

Then again, he never expected to be studying brain tumours at all.

Schramek’s research focused mainly on the biology of breast, pancreas, and head/neck cancers when he joined Mount Sinai Hospital’s Lunenfeld-Tannenbaum Research Institute (LTRI) in 2015.

But when a close family member was diagnosed with a low-grade glioma — a brain tumour that arises from the brain’s glial cells — that same year, he decided to read up on it. He found that little was known about how these tumours developed because they were notoriously difficult to model in the lab. So, with support from OICR’s Brain Cancer Translational Research Initiative, he co-led a study to develop the world’s first mouse model for low-grade gliomas.

“It was a very hard experiment and a bit crazy, honestly,” says Schramek, now a Senior Investigator at LTRI and Associate Professor of Molecular Genetics at the University of Toronto. “Maybe the diagnosis in my family was motivation to see it through.”

Dr. Daniel Schramek

Seven years later, the world-first mouse model is complete, and the study has led to major developments in our understanding of these tumours. As published recently in the journal Science, Schramek and colleagues at LTRI and the Mayo Clinic fine-mapped and characterized a genetic variant (named ‘rs55705857’) that makes people six times more likely to develop low-grade gliomas and causes tumours to develop much earlier.

Their discoveries about the rs55705857 variant being a driver for low-grade gliomas are significant for a few reasons. First is where they found it.

The rs55705857 ‘single nucleodite polymorphism’ is a naturally occurring germline variant, meaning it is present in the DNA of parents’ egg and sperm cells, as opposed to somatic mutations, which arise in other cells after conception and are more commonly associated with cancer. This means that the variant Schramek and colleagues identified, and its implications for cancers, are inherited.

“This is really the first time the inherited component of these tumours has been unraveled,” Schramek says.

It was also surprising to find such a significant cancer-associated variant in a part of the DNA that does not code for proteins. Together with the team at the Mayo Clinic led by Dr. Robert Jenkins, co-senior author of the study, Schramek showed that the variant is in a DNA regulatory region that provides the instructions to fine-tune the expression of essential proteins. However, these regulatory regions are largely understudied and were long considered unimportant.

“We used to think these variants were just noise, but it turns out these seemingly inconsequential variants can actually have a big influence on the likelihood of developing cancer,” Schramek says.

Establishing causality is another important aspect of their findings. It’s one thing to discover that a DNA mutation is linked with cancer risk. But Schramek and colleagues went one step further by demonstrating that this variant actually contributes to causing glial tumours. Their findings suggest that a back-and-forth interaction between germline mutations like rs55705857 and somatic mutations triggers tumour growth.

“Though some cancer-associated mutations are actually very common, they seem to be held in check unless a person has an unfavourable germline set up,” Schramek says.

Findings about rs55705857 are also notable for the mutation’s surprisingly strong association with cancer — a sixfold increase in risk. Most cancer-associated gene mutations only increase risk by one to two times. The only known germline mutation with a comparably high risk is BRCA1, which dramatically increases a woman’s chance of developing breast and ovarian cancer.

Knowledge about BRCA1 and its link to breast cancer has led to targeted screening programs, and Schramek says findings about rs55705857 could spark similar programs for brain cancer. As soon as Schramek found out about the genetic components of low-grade gliomas, he asked his doctors for a brain MRI. Thankfully, the results were negative.

Schramek’s family member underwent surgery that removed most of their brain tumour. The remaining tumour is now dormant, but Schramek says it’s possible it will start growing again in the future. Though low-grade gliomas are less deadly than some other brain tumours, they are difficult to fully remove with surgery. And if they come back, they can evolve into a higher-grade disease.

Schramek and colleagues are now working to understand what causes that progression from low- to high-grade tumours. They are also applying what they learned about the causes of low-grade gliomas to explore therapeutic targets that could give patients more treatment options in the future.

At the moment, Schramek says the biggest implications of this work are for prevention and early detection. Finding brain tumours early is crucial to successfully treating them, and targeted screening could help treat more people earlier and spare others from unnecessary brain surgeries.

“The best cure is to get tumours out early, or even prevent them,” Schramek says. “And I think this new knowledge could be an important step in the right direction.”

Cancer research community loses a pillar of patient partnership in Jill Hamer-Wilson

Jill Hamer-Wilson, who was a tireless advocate for lung cancer patients and a prominent patient partner in cancer research, passed away in November 2022. She served on OICR’s Patient and Family Advisory Council (PFAC) and also worked with the Canadian Cancer Trials Group, the International Lung Cancer Foundation, Canadian Cancer Clinical Trials Network, the Canadian Cancer Society and the White Ribbon Project.

“Jill’s contributions to cancer research were amazing and we are so proud to have had her as part of the OICR family,” says Dr. Laszlo Radvanyi, President and Scientific Director, OICR. “She helped demonstrate the immensely positive impact that patient partners can bring to cancer research. She will be missed greatly here at OICR and in the broader cancer research community. We send our deepest condolences to Jill’s family and friends.”

Jill was diagnosed with stage four lung cancer in 2013 and eventually participated in a clinical trial, which introduced her to the world of cancer research and was the springboard to becoming involved in patient partnership. Since that time Jill touched many lives and used her tenacity and intelligence to create a lasting impact both on researchers and patients.

Despite her health faltering recently, she remained committed to her work, driven by a belief that “research matters” and that patients must help shape it for the better. Jill will be remembered for her thoughtfulness and compassion, her unrelenting advocacy, her supportive voice and enthusiasm, and her effusive smile.

Upon news of Jill’s passing, many tributes were shared, some of which can be read below. You can also learn about Jill’s journey through her blog Through the Valley.

“As an OICR PFAC colleague of Jill’s, I was saddened to hear of her sudden passing. Despite a long and challenging struggle with a devastating lung cancer diagnosis, she continued to persevere and make significant contributions as a cancer patient advocate. Jill was a bright, brave, driven, and supportive individual whose work will continue to inspire hope in those suffering from devastating cancers. All delivered with an ever-present warm smile. She will be sorely missed!” – Terry Hawrysh, Member, OICR PFAC

“Jill had a quiet presence while simultaneously making a massive impact. Her demeanor was always kind, enthusiastic, and encouraging. I very much admire all of the work she did. She contributed so much to the research community and I know that her legacy will live on for a very long time.” – Emily McIntosh, Member, OICR PFAC

“Jill will always be an inspiration. She made a clear choice to spend her precious time helping others, through supporting research and advocating for patients, even while enduring difficult times herself. It was an honour to work with her, although a too brief one.” – Justin Noble, Lead, Patient Partnership and New Initiatives, OICR

https://twitter.com/rtamarchak/status/1592517828606828545?s=20&t=EG2VPYIwgmc31wncnEuMTg
https://twitter.com/iamcatherinela/status/1591856557460946944?s=20&t=EG2VPYIwgmc31wncnEuMTg
https://twitter.com/Dollybrad/status/1591865849769783296?s=20&t=EG2VPYIwgmc31wncnEuMTg

Navigating hope: Helping cancer patients find and enrol in clinical trials

A Windsor-based ‘Clinical Trials Navigator’ program aims to boost trial participation among Canadian cancer patients.

Clinical trials represent hope for many cancer patients, offering access to promising new treatments and a chance to impact the future of cancer care.

Yet only seven per cent of Canadians with cancer end up enrolling in a clinical trial, and the rate is even lower in small cancer centres that run fewer trials than larger hospitals.

Windsor Regional Hospital (WRH) Medical Oncologist Dr. Caroline Hamm has spent years investigating why more people don’t participate in clinical trials and exploring ways to increase patient accrual.

“There are many complex barriers,” says Hamm, who is also the Director of the Windsor Cancer Research Group. “Your access to trials depends on where you live and if you meet eligibility criteria, and patients are often left to search for trials on their own.”

Dr. Caroline Hamm

With support from the Canadian Cancer Clinical Trials Network (3CTN), Hamm has led a unique program out of WRH to help connect cancer patients with relevant trials. Developed with former WRH Board Chair and cancer patient Ron Truant, the program created the Clinical Trials Navigator, a specialist role dedicated to helping people find their way through a clinical trials system that can be difficult to navigate.

As part of the pilot phase, a part-time Clinical Trials Navigator worked with 118 cancer patients who either self-referred or were referred by their oncologists. The Navigator reviewed their medical records and systematically searched for trials that fit their needs. All referrals received a report summarizing information about any eligible trials matching their cancer diagnosis and were contacted for follow up to address questions and track referral outcomes, including trial enrollment.

Though the Navigator took referrals from across the country, most came from smaller population centres like Windsor, where as few as three per cent of cancer patients take part in trials.

As of the end of the pilot, about seven per cent of participating patients — all from smaller cancer centres — ended up enrolling in a trial, which is line with the overall average of both small and large cancer centres.

In a journal article published recently in Cancer Control, Hamm and colleagues concluded that the Clinical Trials Navigator program has the potential to increase patient accrual and close gaps in the in the clinical trials system.

“I think the program has the right idea, but there’s still a lot of work to do,” Hamm says.

She has since expanded the Clinical Trials Navigator program and is digging deeper into the barriers preventing patients from participating in clinical trials. The program now has six navigators (all medical and graduate students) who have helped a total of 240 cancer patients, focusing on areas outside of Toronto to address what Hamm calls the “postal code barrier” to trial participation.

Navigators spend time asking patients questions about what they want out of a clinical trial, what sort of treatments interest them and how far they can travel to participate.

“That kind of back and forth with a patient is a really important part of the experience,” Hamm says.

Hamm and the navigators are also examining the clinical trials system and looking for ways to improve. They are working with a company to start their own searchable clinical trials database they hope will be more user friendly for patients.

Stephen Sundquist is Executive Director of 3CTN, which supported Hamm’s pilot program as part of its mission to increase recruitment to clinical trials and reduce impediments to trial access.

Stephen Sundquist

“Results from the Ontario-led Clinical Trials Navigator pilot have provided useful insights into how the availability of this value-added service can be implemented and scaled up to support greater access to cancer clinical trial options for a wider community of patients and caregivers across Canada who stand to benefit,” says Sundquist, who is also a co-author of the Cancer Control article.

As she looks to further expand the Clinical Trials Navigator program, Hamm is encouraged by the gratitude she has received from patients who participated.

“We got rave reviews from everyone,” she says. “Patients say it means a lot to them to have someone help them during such a difficult time.”

The Next Generation: Nick Cheng is looking for early signs of cancer

As a PhD candidate in Dr. Philip Awadalla’s lab, Cheng is studying blood biomarkers to find cancer years earlier than it is currently detected.

Nick Cheng knew early on that he wanted his research to have a clinical impact. And with his interest in genetics and how our genes shape the way we age, cancer research was a natural fit.

Cheng is applying those interests as a PhD student in Dr. Philip Awadalla’s lab, profiling blood samples for early signs of cancer. While research into blood biomarkers is common, Cheng’s research is unique in that the blood samples he is studying were taken several years before patients were diagnosed with cancer.

“What we could potentially do…is not only detect cancers that aren’t routinely screened for, but also detect them at a stage where they’re highly treatable and survival rates are significantly higher,” Cheng says.

Breaking through the blood-tumour barrier to better treat brain cancer

OICR-supported research has reshaped our understanding of the cellular barrier that makes it difficult to treat medulloblastoma.


New discoveries about the nature of the blood-tumour barrier could help overcome one of the biggest challenges in treating brain tumours.

A team led by Dr. Xi Huang at The Hospital for Sick Children (SickKids) and supported by OICR’s Brain Cancer Translational Research Initiative looked closely at the blood-tumour barrier, a cellular structure that often blocks chemotherapy drugs from killing the cells of brain tumours like medulloblastoma.

In a study published recently in the journal Neuron, they found that the biology of the blood-tumour barrier in medulloblastoma is more unique than previously thought, made up of different cells than the blood-brain barrier that protects normal brain cells.

Huang and team showed that the medulloblastoma blood-tumour barrier is in part directly constructed by tumor cells, a process that requires the ‘Piezo2’ ion channel. By silencing Piezo2 in mice, they were able to stop the barrier from forming, allowing chemotherapy drugs to more effectively attack medulloblastoma cells.

“Our discoveries represent a breakthrough in the understanding of how the blood-tumor barrier forms and works,” says Huang, a Senior Scientist in SickKids Developmental & Stem Cell Biology program. “Our research illuminates a path to overcome the blood-tumour barrier and more effectively treat devastating brain tumours in children.”

Huang’s study is the result of a largescale collaboration that began seven years ago and has yielded multiple new discoveries about how to target and treat brain tumours. The project was also supported by the Arthur and Sonia Labatt Brain Tumour Research Centre, Garron Family Cancer Centre, Sontag Foundation, Cancer Research Society, Canadian Cancer Society, b.r.a.i.n.child, Meagan’s HUG, Ontario Early Researcher Award, American Brain Tumor Association Discovery Grant, Natural Sciences and Engineering Research Council Discovery Grant, Canadian Institutes of Health Research Project Grants and SickKids Foundation. 

“Due to the blood-tumour barrier, chemotherapeutic drugs are often used at high dosages that result in toxicity yet provide limited efficacy. Our study, which benefited from collaborations with other OICR-supported research teams, brings to light a tangible approach to tackle this obstacle. These findings will help us develop more effective treatments with less side effects to benefit brain cancer patients.” Huang says.


This story was adapted from a news release by The Hospital For Sick Children (SickKids).