April 23, 2019
OICR’s Dr. Jared Simpson and collaborators at the University of Oxford create a new method that allows researchers to explore the fundamental, but hard-to-study biological process of DNA replication
How DNA replicates in a cancer cell is difficult to understand, in large part due to the limitations of current technologies. Nanopore sequencing – a fast, portable way to read very long molecules of DNA – could allow researchers to detect DNA replication patterns. Experts in DNA replication from Oxford University, led by Drs. Carolin Müller, Michael Boemo and Conrad Nieduszynski, teamed up with OICR’s expert in nanopore sequencing, Dr. Jared Simpson, to tackle this challenge.
Together, they developed D-NAscent, a sophisticated laboratory protocol and computational tool that together allow researchers to detect and study how DNA is replicated. Recently, the group’s techniques were published in Nature Methods.
“Traditional methods of studying DNA replication have limited resolution – how finely we can see these patterns,” says Simpson, an Investigator at OICR, who helped develop the computational methods used in the study. “With our methods, we can now look at DNA replication on individual, long molecules of DNA at high throughput. This gives us the ability to look for biological patterns that we were once unable to see, for example, in repetitive areas of the genome.”
In the study published today, the group used their methods to study yeast cells, which have a simpler and smaller genome than human cells. Now, the group will apply D-NAscent to study the DNA replication dynamics of human cancer biology. They’ve released their software freely to allow other researchers to do so as well.
“We’re very excited to apply D-NAscent in human cancer cells,” says Simpson. “The potential of this technology is what excites me. We’ve opened up an entirely new way to look at genomic diseases – one that can potentially turn an unexplored aspect of biology into new cancer research discoveries.”
April 23, 2019
Learn about how the Ontario Tumour Bank evaluates the quality of tumour samples stored at ultra-low temperatures over the last decade.
April 18, 2019
OICR is proud to welcome Dr. Sagi Abelson to its Computational Biology Program as a Principal Investigator. Here, Abelson discusses some of his past successes, including his recent leukemia research and his wide range of research interests.
How have you been involved with OICR in the past?
I came to Toronto and joined Dr. John Dick’s lab at the Princess Margaret Cancer Centre as a Postdoctoral Fellow, where I had the opportunity to work with OICR’s Genomics and Genome Sequence Informatics teams. I was investigating the differences between normal aging cells and the cells that lead to leukemia. To do that, we had to look into blood-derived DNA samples from many individuals that develop leukemia following blood collection and search for common genetic markers that indicated a high risk of developing leukemia. I worked closely with OICR teams to prepare and sequence these patient samples. We also collaborated to deploy specialized methodology that enabled us to accurately interpret the genomic data and to identify those harmful mutations.
What motivated you to become involved with that subject?
Far too many patients are diagnosed with leukemia when it is too late. This applies to many other cancers as well. If we can detect a disease earlier, we may benefit from a larger window of opportunity to prevent, manage, or treat the disease. There are many biological and computational challenges that need to be addressed in this area, including finding extremely small traces of a disease amidst a lot of noise in genomic data. I’m interested in the development and the optimization of methods and computational tools to find these first traces of a developing disease.
What will your future research focus on?
In the future I would like to expand my research program to other types of cancers. I truly believe that as a researcher I can achieve more by having a multidisciplinary team that address questions in other biological systems as well. In this era of big data, we are not the only ones realizing that multiple research skills are necessary to tackle the toughest problems. Research institutes and universities understand it as well and therefore introduced computational courses in their biology curricula. That said, conducting research is a team effort and collaboration is the key to approaching scientific problems in areas where you don’t have the expertise.
When approaching the end of your postdoctoral studies and deciding the next step in your career, what opportunities were you considering?
Well, I was looking for a combination of things. I was looking for a place that shares the same vision as I do, the same values of collaboration and translation and a place that has a high caliber of scientists. I believe in the things that OICR works on and how research is done here, so I think it’s a great fit.
What advice would you give to aspiring academics?
To do research well, you first need to love it. You need to be curious, know to identify the needs and ask the right question at the right time. Furthermore, you have to have persistence. You cannot give up in the pursuit of new knowledge.
April 17, 2019
Collaborative research group identifies new cancer-driving mechanisms in brain cancer stem cells, describes novel ways to overcome the limited effectiveness of standard therapy
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.
“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.
April 11, 2019
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.
“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.”
April 9, 2019
Monique Albert, Director of the Ontario Tumour Bank (OTB) explains how OTB provides cancer researchers with the high-quality biospecimens and data they need for their studies.
April 9, 2019
Entrepreneurs from Ontario’s Nanology Labs and Xpan Inc. receive FACIT investment for early-stage cancer innovations
Latest recipients slated to accelerate Ontario’s commercialization momentum are a 2018 finalist and 2019’s winner of FACIT’s Falcons’ Fortunes pitch competition
TORONTO, ON (April 8, 2019) – FACIT, an Ontario First business accelerator and investor for oncology innovations, is pleased to announce recent successes in its mission to help bridge the capital gap often experienced by early-stage entrepreneurs. The newest recipient of FACIT’s Prospects Oncology Fund is Nanology Labs, a start-up based out of the University of Toronto.
Nanology has developed an innovative low toxicity MRI contrast agent that circumvents the limitations of other MRI contrast agents currently available. This exciting nanoparticulate system leverages manganese to illuminate early stage tumours, including those in the brain, in a manner that allows clinicians to make better treatment decisions. Concurrently, it produces oxygen molecules in the tumour which enhances therapeutic efficacy of irradiation. “This seed funding is critical in enabling our technology to reach its next inflection point, moving our system closer to the clinic and positioning our company for further investment,” said Dr. Mohammad Ali Amini, CEO and Co-Founder of Nanology. “We were fortunate to have been chosen as a finalist in FACIT’s 2018 pitch competition, which helped to strengthen our subsequent application to the Prospects Fund.”Continue reading – Entrepreneurs from Ontario’s Nanology Labs and Xpan Inc. receive FACIT investment for early-stage cancer innovations
March 27, 2019
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.
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.
March 26, 2019
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.
March 19, 2019
Collaborative research group performs the most comprehensive analysis of curable prostate cancer to date, finds key connections between different data types
As cancer researchers delve deeper into different omics studies, and technologies enable their ability to do so, it is becoming increasingly important to understand how these areas of research are interconnected. Previous studies across multiple omes – such as the genome, proteome, transcriptome or epigenome – have led to important discoveries in colorectal cancer and ovarian cancer, but prostate cancer remains largely unresolved. Researchers from the Canadian Prostate Cancer Genome Network (CPC-GENE) set out to unravel some of these mysteries.
In the most recent CPC-GENE study, published today in Cancer Cell, the research group integrated multiple levels of omics analyses to better understand the biology of intermediate-risk prostate cancer – a type of cancer in which it is notoriously difficult to predict and treat accordingly. A better understanding of this disease could lead to improved tests that can determine which tumours are aggressive and require aggressive treatment, while helping spare those whose cancer will never become aggressive the negative side effects of treatment.
“We cannot overlook the important information that we gain from looking at the bigger picture,” says Julie Livingstone, bioinformatician at OICR and co-author of the study. “In this case, this means looking at prostate cancer from multiple angles – or multiple omes – to potentially find new markers of aggressive disease.”
The study explored 76 prostate cancer tumours and found new combinations of information that could act as a better predictor of a patient’s chance of relapse than any single piece of information alone. More specifically, they identified that the combination of protein and methylation data could, on average, predict the severity of a tumour better than looking at just the proteins – the proteome – or just the methylation patterns – the methylome – alone.
“Integrating datatypes is anything but straightforward, but it illuminates interesting aspects about prostate cancer that we haven’t seen before,” says Livingstone. “In the future, we intend to pursue our multi-omic investigation and translate this understanding into better tools to inform treatment selection for men with this disease.”
Find out more about research from the CPC-GENE project on OICR News.
March 15, 2019
Expert researchers find shorter treatment cycles may reduce risk of breast cancer returning
Researchers have found that the dosage and interval of chemotherapy treatments have a significant impact on some breast cancer patients’ survival. For a very small minority of patients the difference of a week between chemotherapy treatments could mean the difference between life and death – and researchers are working to identify exactly who those patients are.
Over the last few decades, breast cancer clinical trials have investigated the way in which patients receive and respond to different chemotherapy dosing regimens. Some have tested if a shorter – but more intense – two-week treatment cycle is more effective than the standard three-week cycle. These trials, however, are often limited in size and do not have the statistical power to detect a difference in response to treatment.
Researchers from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) have recently performed a meta-analysis across 26 breast cancer trials to help clarify this dosing dilemma. As reported in The Lancet, they found that more intense dosing regimens were associated with a decreased risk of death from breast cancer and a decreased risk that the disease will return in some patients.
“As chemotherapy kills tumour cells, the residual – or remaining – cancer cells have more room to grow and tend to grow faster,” says Dr. John Bartlett, Program Director of Diagnostic Development at OICR and member of the EBCTCG Steering Committee. “These trials hypothesized that a more intense dosing regimen would give tumour cells essentially less room to grow. With the results of the EBCTCG overview study, we can say with confidence that a two-week treatment schedule will help to prevent death in a small portion of patients.”
The analysis found that approximately one in 50 women benefited from more intense dosing.
“The challenge now is to determine exactly which patients can benefit from intense dosing and which patients would not,” says Bartlett.
“If we can do so, we can prevent deaths due to breast cancer for some, while minimizing the negative side effects of intense chemotherapy for others.”
The ECBTCG is continuing to investigate dosing intensity in common breast cancer subtypes in parallel with researchers who are looking to find the biological basis of these differing responses to treatment.
“We’re in an era of de-escalation where we’re heavily invested in reducing overtreatment,” Bartlett says. “But this work helps us move towards an era of biologically rational treatment recommendations, one where breast cancer patients get the treatment they need at the right time and in the right way.”
March 13, 2019
Researchers begin to unravel why some prostate tumours can be seen with magnetic resonance imaging and others go undetected
Determining whether a patient with prostate cancer requires aggressive therapy or active surveillance is a growing challenge for the healthcare system. Blood tests can detect early signs of prostate cancer, but these tests can lead to many unnecessary and painful biopsies for patients whose disease never becomes aggressive.
Multi-parametric magnetic resonance imaging (mpMRI), a type of non-invasive imaging technique, has the potential to help determine which patients require biopsies and which can be spared possible negative side effects, such as bleeding, pain and infection. Some tumours are visible by mpMRI while some are not, yet it’s not well understood if this visibility can predict a tumour’s aggressiveness.
Researchers at OICR have teamed up with clinicians from the University of California, Los Angeles to investigate the molecular properties of MRI-visible and MRI-invisible tumours. In their recent study, published in European Urology, they found that visible tumours have similar features to aggressive tumours and discovered new features that may be contributing to the disease’s aggression.
“Even if two tumours are similar in size and in similar positions, one still may be MRI-visible and one may be MRI-invisible,” says Kathleen Houlahan, PhD Candidate at OICR and lead author of the study. “We wanted to see if this visibility could help us determine if a cancer is aggressive, so we took the first step towards unraveling the relationship between a patient’s MRI results and the molecular characteristics of their tumour.”
Recent commentary on the study highlights Houlahan’s work as an “initial foray” into the intersection of radiology, pathology and genomics, but recognizes the limited size of her exploratory study. Recent MRI-focused clinical trials will provide larger datasets for further investigation.
“If we can better understand why some tumours show and some don’t, we could potentially use imaging to predict the course that a patient’s disease will take,” says Houlahan. “Ultimately, we hope that this technique can help reduce unnecessary prostate biopsies and ensure that the men who need treatment get the treatment they need.”