October 7, 2020
Vivian talks about the research that OICR is doing during COVID-19 and the kinds of safety precautions that OICR is taking.
September 24, 2020
OICR-supported researchers discover new way to match advanced pancreatic cancer patients with the most appropriate treatment for their disease
Over the next 10 years, it is expected that pancreatic ductal adenocarcinoma (PDAC) will become the second leading cause of cancer-related deaths in North America. Precision medicine for PDAC is dependent on understanding which cancers will respond to treatment and which will not, but progress in this space has been limited by challenges including the complexity and severity of the disease. With more than 10 years of clinical and genomic data from the COMPASS trial, OICR-supported researchers have recently discovered a new, simplified way to match patients with the most appropriate treatment for their disease by measuring the expression of two genes, GATA6 and Keratin 5. Their discovery was recently published in Clinical Cancer Research.
“Even with current chemotherapies, patients diagnosed with PDAC have a median survival of one year,” says first author Dr. Grainne O’Kane, Medical Oncologist at the Princess Margaret Cancer Centre. “This work is dedicated to extending the lives of these individuals.”
The study group discovered that by measuring the expression of GATA6 and Keratin 5 in a patient’s tumour sample, they can differentiate subtypes of advanced pancreatic cancer. The different subtypes of the disease tend to respond to treatments differently, so clinicians and patients could potentially use this information to help guide treatment selection.
More specifically, the group showed cancers with low GATA6 expression and high Keratin 5 expression tend to be resistant to mFFX, one of the usual chemotherapy regimens. The study highlights the need for new, effective treatments for these patients.
“To discover these specific genes, we used sophisticated sequencing and in-depth analyses, but what we’ve found is that this classification can be done using simpler, widespread pathology techniques,” says senior author Dr. Sandra Fischer, Staff Pathologist at University Health Network. “This is promising because these discoveries can be easily applied in the clinic, and translated into patient care.”
The article was selected by Clinical Cancer Research to be highlighted on the front cover of the September 2020 issue and featured as one of the Issue Highlights.
Through the COMPASS trial, the researchers plan to further evaluate and validate this classification technique.
“I’m proud to be part of this team,” says Fischer. “Every step we take is a stride forward towards more precision and effective treatment for patients with this devastating disease.”
In December 2015, PanCuRx launched a clinical trial called Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection: A Prospective Study (COMPASS). The trial is designed to show that the sequencing of pancreatic tumours can be performed in a clinical setting and results delivered within a clinically-relevant timeframe to help guide treatment for individual patients. Read more on the latest COMPASS findings.
September 21, 2020
Q&A with new OICR Investigator Dr. Anastasia Tikhonova on tackling cancer cell cross-talk and adapting in a rapidly evolving field
OICR welcomes Dr. Anastasia Tikhonova to Toronto as an OICR Investigator and Scientist at the Princess Margaret Cancer Centre
The pandemic has compelled many people to adapt, and researchers are no exception. For Dr. Anastasia Tikhonova, adapting has always been an essential part of her career.
Tikhonova recently joined the OICR community as an OICR Investigator working at the Princess Margaret Cancer Centre. Her research focuses on hematological malignancies – or blood cancers – and how the environment around these cells can regulate their growth or help them resist standard treatments. Her research in this area will support the development of new cancer therapies that can ultimately help patients live longer and healthier lives.
Here, she describes her research program and why this community is a great place for her.
What is your research all about?
AT: Cancer cells do not exist in isolation. They are surrounded – and influenced – by their healthy neighbouring cells. For a long time, we didn’t fully understand the interactions between a cancer cell and its surrounding environment and how this dialogue impacts tumour growth. The last five years have significantly advanced imaging and genomic technologies that allow us to precisely decode the cross-talk between diseased cells and their environment – or their niche.
This is what my research is all about. My team uses single-cell transcriptomics, high-resolution imaging, and functional genomics to understand the connection between the complex elements in the bone marrow and cancer. Our goal is to untangle these connections and devise new strategies to target the interaction between leukemic cells and their environment, with the goal of eliminating blood cancers.
What got you interested in this space?
AT: I was fascinated by biology as a child. I remember learning about evolution in my first biology class in the fifth grade – I have been hooked ever since! I love being in the lab. I am exhilarated by seeing results for the first time and being able to connect the dots between different experiments. When I recognize a gap in my understanding, I feel compelled to learn more. This is how I became interested in the stem cell niche and leukemic microenvironment. As a Postdoctoral Fellow, I was fortunate to have had the opportunity to work in a top hematopoietic lab where I started to scratch the surface of understanding the niche’s molecular architecture, but many questions remain. Continuing this line of inquiry, I look forward to translating my findings into innovative therapies here in Ontario.
Why did you choose to come to Ontario?
AT: Princess Margaret is one of the top cancer research centres in the world. During my recruitment I had an amazing experience interacting with the faculty and trainees here. They were highly engaged and asked great questions, indicating a rich intellectual environment. Since most of my ideas come to me when I am working with others, this is the ideal place for my young lab to grow intellectually. Plus, the people here are genuinely supportive. My move was delayed due to COVID, but everyone here has been exceptionally helpful.
How has COVID impacted your work?
AT: An important trait to have as a scientific researcher is agility or the ability to quickly adapt to changing environments. Furthermore, COVID made me realize that nothing can shake my enthusiasm for starting a research group.
As a result of pandemic, I think people have become more open to collaboration. In some ways, online communication has leveled the playing field, bringing geographically distant researchers into the same space as colleagues accustomed to side-by-side interactions.
I also think COVID has brought science into public view. For the first time in my life, I hear immunology terms on the morning news. I’m excited by the prospect of biomedical research being a common discussion topic.
Does your work apply to other diseases?
AT: Yes, it does. I have a specific focus in a rare form of leukemia, called T-ALL. My research applies to other cancers as well. Insights from one disease can often guide our understanding of other malignancies.
Notably, my research in the regenerative medicine space of the bone marrow niche has the potential to impact thousands of patients treated every year with bone marrow transplantation. Additionally, if we can better understand how to regenerate the bone marrow microenvironment, we could bring a whole new treatment paradigm to patients with a wide spectrum of benign and malignant diseases. At the end of the day, this is what it’s all about.
September 16, 2020
Scientists discover mechanism of bone loss caused by acute lymphocytic leukemia, identify targeted therapy for children
OICR-supported research team discovers new pathway through which leukemia cells damage bone and a treatment that may protect children with leukemia from these effects
Due to remarkable progress in the treatment of pediatric leukemias with multi-drug chemotherapy, upwards of 85 per cent of children with the disease survive. One consequence of this success, is that more than a third of these patients suffer from in-bone fractures and pain during leukemia and for years following their treatment. In a recent study, Ontario researchers at the Hospital for Sick Children (SickKids) have discovered a process by which leukemia cells damage bone and discover that a targeted therapy may be able to prevent this damage.
In their study, published in Science Translational Medicine, the research group discovered that the bone degradation in leukemia patients is triggered by a protein called RANKL on the surface of the leukemic cells interacting with receptors called RANK on the surface of bone-degrading cells. The group showed that a drug, which is similar to one that is currently in clinical trials for other cancers, could specifically block this RANKL-RANK interaction and prevent further bone damage.
“A pan-Canadian study demonstrated that 15 per cent of children display bone fractures at the time they are diagnosed with acute lymphocytic leukemia, or ALL,” says lead author Dr. Jayne Danska, Senior Scientist in the Genetics & Genome Biology program at SickKids and Associate Chief, Faculty Development and Diversity at the SickKids Research Institute. “In addition, standard ALL chemotherapy protocols include corticosteroids which further damage the bone. Survivors of childhood ALL experience fractures and pain, and some cases are so severe that they require a hip replacement in their teenage years. We have discovered one mechanism that contributes to ALL-associated bone damage and a potential way to prevent it.”
To make these discoveries, first author of the study, Dr. Sujeetha Rajakumar, a postdoctoral fellow at SickKids, transplanted ALL cells from patient donors into experimental mouse models to examine the effect of leukemia cells on bone and how to disrupt the RANKL-RANK interaction. This so-called xenotransplantation method was pioneered by Dr. John Dick at the University Health Network’s Princess Margaret Cancer Centre.
Using these animal models, Danska’s group showed that treatment of the ALL-transplanted mice with a protein therapeutic that blocks the RANKL-RANK interaction prevented bone damage despite high number of leukemia cells in the bone compartments.
“There are clinical trials underway to test whether RANKL-RANK antagonists can prevent bone degradation in adults with metastatic prostate and breast cancers,” says Danska, who is also a Professor in the University of Toronto’s Faculty of Medicine. “The data we report in the human ALL transplant model is encouraging because the availability of clinical data with this class of drug can accelerate application of our discoveries to clinical trials in youth with ALL.”
“Children with leukemia sustain unbelievably rigorous and lengthy chemotherapy treatments,” says Danska. “We’re eager to bring our discoveries into clinical trials that may help minimize these painful and life-altering late effects of this disease.”
Danska and study collaborators Drs. Cynthia Guidos and Johann Hitzler of SickKids, and Drs. Mark Minden and John Dick of the Princess Margaret Cancer Centre are members of OICR’s Acute Leukemia Translational Research Initiative (TRI), which partially funded the study.
September 16, 2020
This post was edited and republished with the permission of CanPath.
CanPath is pleased to announce that, with funding support from the Canadian Partnership Against Cancer, a Saskatchewan cohort will be developed and join the CanPath study. The Saskatchewan Partnership for Tomorrow’s Health (Saskatchewan PATH) will add approximately 9,000 participants to the existing cohort of over 330,000 Canadian participants. The addition of Saskatchewan means that all 10 Canadian provinces have now joined CanPath.
Saskatchewan PATH will create a platform and resource for fostering research in cancer and chronic disease prevention within the province. The Saskatchewan PATH study will be led by Scientific Director, Riaz Alvi and hosted by the Saskatchewan Cancer Agency.
“We are excited to officially welcome Mr. Alvi and the Saskatchewan PATH team to the CanPath partnership. We look forward to working together to develop a truly pan-Canadian study and sharing learnings from our other regional cohorts to support Saskatchewan PATH as they move forward,” says John McLaughlin, Executive Director of CanPath.
“We are proud to be a part of this truly national program. Saskatchewan holds a prominent place in the history of healthcare in Canada, and houses one of the world’s oldest cancer registries. We are confident that the people of Saskatchewan will welcome this opportunity to participate in Saskatchewan PATH to help further a better understanding of cancer and other chronic diseases, and to assist with the future development of prevention, early detection, diagnosis and treatment programs. There is exciting and highly rewarding work ahead of us.” says Riaz Alvi, Scientific Director of Saskatchewan PATH.
Saskatchewan has a unique and diverse population, with roughly half living in the province’s largest city, Saskatoon, or the provincial capital of Regina. The province’s economy is primarily associated with agriculture and more recently mining. The burden of cancer in Saskatchewan is significant with about 5,600 new cancers diagnosed in 2018 and just over 2,000 cancer deaths in the same year. In 2018, the number of people living with cancer that had been diagnosed within the last 5 years (5-year prevalence), was approximately 17,000 people.
“Since CanPath began almost 11 years ago, we have sought to ensure representation of all provinces. Now being able to include participants from the province of Saskatchewan fills an important gap, and builds upon the hard work of many of us who started and have maintained the CanPath cohort and vision since the beginning,” says Philip Awadalla, National Scientific Director for CanPath.
With CanPath’s guidance and support of the development of Saskatchewan PATH, the new cohort will benefit from the experience and lessons learned by CanPath’s other regional cohorts. Saskatchewan PATH joins the six regional cohorts that currently makeup CanPath: BC Generations Project, Alberta’s Tomorrow Project, Manitoba Tomorrow Project, Ontario Health Study, CARTaGENE (Quebec), and Atlantic PATH.
The development of Saskatchewan PATH will consist of three phases:
- Phase I – Planning & Implementation (Present to March 2022)
- Phase II – Participant Recruitment and Collection of Data and Biological Samples
- Phase III – Maintenance and Use of Participant Data and Biological Samples
The Canadian Partnership for Tomorrow’s Health (CanPath) is Canada’s largest population health cohort and a national platform for health research. Comprised of more than 330,000 volunteer participants, CanPath is a unique platform that allows scientists to explore how genetics, environment, lifestyle and behaviour interact and contribute to the development of cancer and other chronic diseases. CanPath is hosted by the University of Toronto’s Dalla Lana School of Public Health with national funding from the Canadian Partnership Against Cancer. The Ontario Institute for Cancer Research (OICR) hosts CanPath data in a safe and secure environment. To learn more, visit www.canpath.ca.
The original post can be viewed here: https://canpath.ca/2020/09/canpath-completes-provincial-map-with-addition-of-a-saskatchewan-cohort/
September 10, 2020
OICR-supported researcher Dr. Harriet Feilotter leads liquid biopsy research program
As the COVID-19 pandemic has impacted many areas of life, including the diagnosis and treatment of other health conditions, people have chosen to forgo cancer screening and care in attempt to minimize their potential exposure to the virus. Relative to the general population, people living with cancer are more susceptible to the virus, but delaying cancer treatment may allow the disease to grow or spread.
Dr. Harriet Feilotter has teamed up with members of the pan-Canadian Digital Technology Supercluster to bring greater access to cancer testing and treatment during the pandemic and beyond. Through the $2.59 million Project ACTT (Access to Cancer Testing & Treatment in Response to COVID-19), they aim to provide liquid biopsy solutions, which require only a simple blood draw, as alternatives to surgical tissue biopsies for cancer diagnosis and care.
“The goal is to allow patients alternatives to invasive procedures that may be difficult to access during a pandemic,” says Feilotter, Molecular Geneticist and Scientist at Kingston Health Sciences Centre, faculty member of Queen’s Cancer Research Institute and OICR Associate. “Not only would this benefit those patients who live far from large cancer centres, but it could limit patient exposure to COVID-19 and increase health system capacity.”
The collaborative team is led in part by Canexia Health, which develops specialized cancer genomic assays, and Patriot One Technologies Inc.’s subsidiary Xtract AI, which specializes in machine learning solutions across a variety of applications, among other private and public partners. Together, they will work to enhance their current tests that detect mutations in circulating tumour DNA (ctDNA) from blood and deploy these tests for multiple cancer types across Canada.
Now through ACTT, some patients have access to these tests in British Columbia, Ontario, Quebec and Saskatchewan. The long-term objective is to increase access across the country.
“The development of liquid biopsies and ctDNA testing has been accelerated by this pandemic,” says Feilotter. “We’re proud to team up in this cross-disciplinary, cross-sector collaboration to bring these promising solutions to more patients.”
September 3, 2020
OICR-based PhD Candidate awarded University of Toronto COVID-19 Student Engagement Award
When the COVID-19 pandemic shut down labs across Canada, cancer research trainees looked for ways to help respond to the pandemic. PhD candidates Tom Ouellette and Jim Shaw saw an opportunity to combine their skills and contribute to the cause.
Ouellette and Shaw were recently awarded a University of Toronto COVID-19 Student Engagement Award for their project titled Network and evolutionary analysis of SARS-CoV-2: A vaccine perspective. Together, they will develop new machine learning tools to analyze the SARS-CoV-2 genome and how it evolves.
“We’re two like-minded individuals with complementary skillsets who enjoy coding, math and solving problems, which – fortunately – can be done remotely,” says Ouellette, who is a PhD Candidate in Dr. Philip Awadalla’s lab at OICR. “We saw the opportunity to help with COVID-19 research and we’re happy to apply our skills to help advance research towards new solutions for this pressing problem.”
Ouellette specializes in evolution and population genetics and Shaw specializes in network analysis and algorithm development. Through this award, they will investigate how SARS-CoV-2 is evolving by looking into specific regions of the virus’ genetic code from samples around the world, using mathematical modelling, machine learning, and evolutionary simulations. They are specifically interested in how these changes in the genetic code may alter the virulence, or severity, of the virus.
“Just like cancer, different pressures or stresses can make viruses evolve,” says Shaw, who is a PhD Candidate in mathematics at the University of Toronto. “Understanding these changes can have an impact on how we build vaccines. Furthermore, better understanding of the virus’ evolution may shed light on viral reinfection, which is an important issue as we move into the later stages of the pandemic.”
Ouellette and Shaw plan to publicly release the code that they develop through this initiative for other researchers to build upon.
“SARS-CoV-2 has a much simpler genome than a cancer genome, so it can serve as a simplified model to test out new analytical techniques,” says Ouellette. “Ultimately, I hope to bring the tools and technology we create back into my research on cancer so we can better understand how cancer evolves and becomes resistant to treatment.”
August 31, 2020
Learn about the research that the Ontario Health Study has been doing during COVID-19 and how scientists have managed to do this work from home.
August 28, 2020
In the most comprehensive analysis of whole cancer genomes to date, OICR researchers identify novel sex-linked genomic differences that may be able to predict cancer severity and response to therapy
Cancer differs in males and females but the origins and mechanisms of these differences remain unresolved. A better understanding of sex-linked differences in cancer could lead to more accurate tests and allow sex to be included as a consideration when personalizing treatments for patients.
In a study, published in Nature Communications, OICR’s Constance Li and collaborators identify key genetic characteristics that differ between sexes. Here, Li describes what they found and what this means for patients.
Some studies have already hinted that cancer genomes differ between males and females. What is new about this study?
Previous studies focused on the exomes of patient tumours. That means that they were only looking at a small fraction of the genome that codes for proteins. This study allowed us to look at the entire genome – all of our DNA code – and take a dive deep into many aspects of the disease, like how tumours evolve over time.
By looking at the entire genome and in this ‘dark space’ that we hadn’t explored, we were able to confirm some previous findings but also find new differences between male and female tumour samples.
What sort of differences did you find?
We catalogued the differences we found across nearly 2,000 patient tumours representing more than two dozen different cancer types. Interestingly, we found that biliary cancers – like some liver, gall bladder and bile duct cancers – evolve differently in males than they do in females.
We also found that mutations in the TERT promoter – which is a hot topic in cancer research – occur much more often in men than in women, especially in thyroid cancers.
What does this mean for researchers who are looking into this subject?
Our findings suggest that there are underlying biological differences in the way that male and female tumours begin and progress. Overall, we need to be aware of these differences and consider the sex differences as we develop new tools that can match patients to appropriate treatments.
How else could this be helpful for cancer patients?
These findings are preliminary but powerful. It is important to note that more clinical data and research are needed to validate the differences we found. Ultimately, if we look deeper and find that a cancer progresses along one course in females and a different course in males, we can design roadblocks – or therapies – to stop the cancer along that specific course for that sex.
This paper is part of the Pan-Cancer Analysis of Whole Genomes Project. Read more about the Pan-Cancer project here.
August 28, 2020
OICR-supported researchers and collaborators discover indicators in the blood that may predict which patients will respond to the immunotherapy drug, pembrolizumab
Adapted from UHN’s Media Release.
Immunotherapy can shrink tumours and prolong survival for certain cancer patients, but clinicians don’t yet know which patients will benefit from these treatments. OICR-supported researchers and collaborators at the Princess Margaret Cancer Centre have made a discovery that could help identify those patients who may benefit and match them with potentially life-saving therapies.
In their study, recently published in Nature Cancer, the research group found that the changing levels of tumour fragments, or circulating tumour DNA (ctDNA), in a patient’s blood can be used to predict whether they will respond to the immunotherapy drug pembrolizumab.
The study lays the foundation for researchers to develop an easy, non-invasive and quick blood test to determine who will benefit from the drug and how well their disease is responding to treatment.
“While we have known for some time that cancer disease burden can be monitored by measuring tumour DNA in the blood, we are excited to report that the same concept can be applied to track the progress of patients being treated with pembrolizumab,” says co-first author Cindy Yang, PhD Candidate in Dr. Trevor Pugh’s lab at the Princess Margaret Cancer Centre and OICR. “This will hopefully provide a new tool to more accurately detect response and progression in patients undergoing immune checkpoint inhibitor therapy. By detecting progression early, patients may have the opportunity to undergo subsequent lines of treatment in a timely fashion.”
The benefits of blood tests
Conventionally, imaging scans – such as computerized tomography (CT) scans – and other methods are used to monitor a patient’s cancer. This study suggests a simple and quicker blood test as an alternative to these scans.
“Although important, computerized tomography (CT) and other scans alone will not tell us what we need to know quickly or accurately enough,” says senior author Dr. Lillian Siu, Senior Scientist and medical oncologist at the Princess Margaret Cancer Centre.
Dr. Scott Bratman, radiation oncologist and Senior Scientist at the Princess Margaret Cancer Centre and co-first author of the study, points out that it may take many months to detect whether a tumour is shrinking with various imaging scans.
“New next-generation sequencing technologies can detect and measure these tiny bits of cellular debris floating in the blood stream accurately and sensitively, allowing us to pinpoint quite quickly whether the cancer is active.”
This study represents one of the many emerging applications of using ctDNA to guide treatment decisions. It is one of the first to show that measuring ctDNA could be useful as a predictor of who responds well to immunotherapy across a broad spectrum of cancer types.
The prospective study analyzed the change in ctDNA from 74 patients, with different types of advanced cancers, being treated with pembrolizumab. Of the 74 patients, 33 had a decrease in ctDNA levels from their original baseline levels to week six to seven after treatment with the drug. These patients had better treatment responses and longer survival. Even more striking was that all 12 patients who had clearance of the ctDNA to undetectable levels during treatment were still alive at a median follow-up of 25 months.
Conversely, a rise in ctDNA levels was linked to a rapid disease progression in most patients, and poorer survival.
“Few studies have used a clinical biomarker across different types of cancers,” says Siu, who also co-leads OICR’s OCTANE trial. “The observation that ctDNA clearance during treatment and its link to long-term survival is novel and provocative, suggesting that this biological marker can have broad clinical impact.”
Innovation and translation
This study is part of a larger flagship clinical trial, INSPIRE, which has enrolled more than 100 patients with head and neck, breast, ovarian, melanoma and other advanced solid tumours. INSPIRE brings together researchers from many disciplines to investigate the specific genomic and immune biomarkers in patients that may predict how patients will respond to pembrolizumab.
INSPIRE is made possible by collaborations across institutes and industries with expertise from those applying genomics to research and those applying genomics in the clinic.
“INSPIRE is an incredibly collaborative initiative that is a blend of big genomics – looking at large trends across many individuals – and highly-personalized genomics – looking at mutations within each patient sample,” says Pugh, co-senior author, Senior Scientist at Princess Margaret and Senior Investigator and Director of Genomics at OICR. “This is a modern approach to the translation of clinical genomics.”
“As a PhD student, this project gave me the unique opportunity to work in a highly collaborative intersection with industry, clinical, and academic partners,” says Yang. “It is very exciting to see translational research in action.”
Read the UHN Media Release.
August 28, 2020
The tools behind the treatment: Building image-guided devices for more accurate and effective cancer procedures
OICR-supported researchers develop multi-purpose AI algorithm to help track needle placement and improve the accuracy of several image-guided treatment techniques
Cancer patients often encounter many needles, some of which are used to collect tissue samples or deliver therapy directly to a tumour. Specialists who carry out these procedures are trained to place needles precisely in the correct location, but what if we could give these specialists a real-time GPS for needles? Would biopsies be more accurate? Could needle-related therapies be more effective?
Dr. Aaron Fenster’s lab is working to develop tools for these specialists to guide their needles and ultimately improve the accuracy of biopsies and therapies for patients. In their recent paper, published in Medical Physics, they describe their new deep learning method to track needles in ultrasound images in real time.
“It may be surprising to many individuals, but a lot of these procedures are still done based on skill alone and without image processing,” says Dr. Derek Gillies, medical physicist in training and co-first author of the paper. “We’re working to provide clinicians with tools so they can better see their needles in real time rather than going in blind for some procedures.”
The deep learning methods presented in this paper are applicable to many types of needle procedures, from biopsies – where a clinician draws a tumour sample from the body – to brachytherapy – where a clinician delivers radiotherapy directly to the tumour. The methods could also be applied to several cancer types including kidney cancer, liver cancer and gynecologic cancers.
“Developing artificial intelligence algorithms requires a lot of data,” says Jessica Rodgers, co-first author of the paper and PhD Candidate at Western University’s Robarts Research Institute. “We didn’t have a lot of imaging data from gynecologic procedures, so we decided to team up to develop a method that could work across several applications and areas of the body.”
“That’s the most exciting aspect of this effort,” says Gillies. “To our knowledge, we were the first to develop a generalizable needle segmentation deep learning method.”
Now, members of the Fenster lab are working to integrate these algorithms into the video software equipment used in the clinic.
“Our work is giving clinicians new tools, which can help them make these procedures more precise and more accessible,” says Rodgers. “These tools could ultimately help lead to fewer missed cancer diagnoses and fewer patients with cancer recurrence.”
August 25, 2020
OICR-supported researchers demonstrate new drug may eliminate triple negative breast cancer cells in certain patients, discover a new method to identify which patients will benefit
Adapted from UHN’s Media Release.
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that often spreads to other organs and accounts for one in four breast cancer deaths. OICR-supported researchers at the University Health Network’s Princess Margaret Cancer Centre are zeroing in on the molecular mechanisms that fuel this deadly cancer’s runaway growth to develop more effective treatments for this disease.
In their study, recently published in Nature Communications, they found a promising approach that could potentially identify the patients who could benefit from a more precise, targeted therapy for TNBC.
“This disease has no precision medicine, so patients are treated with chemotherapy because we don’t have a defined therapeutic target,” says co-lead of the study Dr. Mathieu Lupien, Senior Scientist at the Princess Margaret Cancer Centre and OICR Investigator. “Initially, it works for some patients, but close to a quarter of patients recur within five years from diagnosis, and many develop chemotherapy-resistant tumours.”
“These savage statistics mean that we must improve our understanding of the molecular basis for this cancer’s development to discover effective, precise targets for drugs, and a companion test to identify which patients are most likely to benefit the most from such a therapy.”
The study investigated how TNBC cells are dependent on a specific protein called GLUT1 and its associated molecular pathways. Prior studies suggested that TNBC cells were dependent on GLUT1, but this study is the first to demonstrate that blocking GLUT1 function may be an effective therapeutic strategy for certain patients with TNBC.
Using a collection of cell lines, the researchers found that blocking this pathway with a drug-like chemical compound “starved” the cancer cells, but only in a subset of TNBC patient samples. The group investigated further and found a common trait between the cell lines that were sensitive to the drug – they had high levels of a protein called RB1. This indicates that patients with TNBC and high levels of RB1 may, one day, benefit from this drug.
“Having access to diverse cell models of triple-negative breast cancer allows us to distinguish where the potential drug will work, and where it won’t,” says Lupien. “Without this broad spectrum of samples, we might have missed the subset of triple-negative breast cancers that respond to our compound.”
Collectively, this study suggests that clinical evaluation of targeting GLUT1 in certain patients with TNBC is warranted.
“The more we understand about the molecular complexity of cancer cells, the more we can target with precision,” says co-lead of the study Dr. Cheryl Arrowsmith, Chief Scientist for the Structural Genomics Consortium Toronto laboratories and Professor of Medical Biophysics at the University of Toronto. “And the more we can build up a pharmacy of cancer drugs matched to specific changes in the cancer cell, the greater the chance of a cure.”
Read UHN’s Media Release.