April 1, 2020
OICR-supported researchers quantify common prostate cancer outcome predictor
Advances in cancer research have opened the door to new tests to better assess tumours and help recommend the most appropriate course of treatment for a patient. Research pathologists play a critical role in turning scientific knowledge into tests that can be used in an everyday clinical setting.
“Scientists are constantly advancing our understanding of cancer, but that understanding cannot help patients unless it’s applied in practice,” says Dr. Tamara Jamaspishvili, Research Pathologist at Queen’s Cancer Research Institute. “Our role as research pathologists is to bridge that gap, and transform discoveries into more accurate diagnoses and prognoses for patients that could be implemented and actionable in practice.” Jamaspishvili’s work is supported by the Ontario Molecular Pathology Research Network, an OICR-funded province-wide network that conducts high-quality cancer research focussed on clinical impact.
An example of the challenge of clinical translation is found in PTEN testing. PTEN is a cancer-preventing gene that – when absent in a cell – may lead to uncontrolled tumour growth. Research has shown that the loss of PTEN within a prostate tumour could help predict the severity of a man’s prostate cancer, but PTEN is not routinely tested.
“Simply put, some cells in a tumour sample may have PTEN loss and some cells don’t, but nobody has clearly quantified how the ratio of cells with or without PTEN contribute to a patient’s health,” says Jamaspishvili.
Jamaspishvili teamed up with collaborators to address the subjectivity of PTEN testing. Her collaborators include Drs. David Berman, Palak Patel, Robert Siemens, Paul Peng, and Yi Niu from Queen’s Cancer Research Institute, Drs. Fred Saad and Anne-Marie Mes-Masson from the University of Montreal, Dr. Tamara Lotan from Johns Hopkins University, and Dr. Jeremy Squire and colleagues at the University of São Paulo.
Their study, recently published in the Journal of the National Cancer Institute, proposes a new quantitative approach to assess PTEN. They clarify how pathologists can predict the severity of a patient’s prostate cancer based on the number of cells with PTEN loss. These findings can help standardize PTEN testing, but their approach can also be applied to other pathology tests that are still highly subjective.
“Quantifying qualitative tests helps us move towards automated pathology techniques,” says Jamaspishvili. “This is the future of pathology.”
Jamaspishvili is now working to automate PTEN digital pathology analysis in collaboration with Dr. Stephanie Harmon and colleagues in Dr. Baris Turkbey’s lab as part of the National Cancer Institute’s Molecular Imaging Program.
“Now, we can apply machine learning image analysis tools to analyze PTEN loss and make better predictions for the benefit of patients. We look forward to using artificial intelligence in digital pathology to help fill the gaps between research and clinical practice.”
December 6, 2019
OICR-funded clinical trial shows value in advanced biopsy techniques for men with low-risk prostate cancer
Many of the 23,000 men across Canada who will be diagnosed with prostate cancer this year won’t need aggressive treatment. Instead, men with low-risk or slow-growing cancers may be offered ‘active surveillance’, where their healthcare team monitors their cancer closely with regular tests, scans and biopsies. Dr. Laurence Klotz, a world leader in active surveillance, is working to improve how surgeons in Ontario and across Canada perform these important prostate biopsies.
Klotz, who is a leading urologic surgeon and researcher at Sunnybrook Health Sciences Centre, teamed up with collaborators in London, Hamilton, Kitchener and Toronto to bring the latest MRI-guided prostate biopsy techniques to patients across the province. With OICR’s support, they evaluated the use of MRI-targeted biopsies, where a surgeon uses MRI images to help guide biopsy needles, relative to traditional biopsies, and found that the use of MRI results in 50 per cent fewer failures of surveillance. The findings from their two-year study were recently published in European Urology.
“As shown in other countries like the U.K. and Australia, using MRI before biopsies can reduce the diagnosis of insignificant cancers, selectively find aggressive cancers and reduce the number of false negatives,” says Klotz. “Our study showed that using MRI allows us to better pinpoint prostate cancers as they progress.”
Learnings from this study have helped inform the design of a new trial, called PRECISE, that is evaluating whether MRI can replace biopsies and spare some men from the associated side effects. Results from PRECISE will be submitted for publication in the next few months.
“We’ve laid the groundwork for better prostate cancer diagnosis,” says Klotz. “This means we’re one step closer to ensuring each man receives the most appropriate treatment for his individual cancer.”
October 7, 2019
International study, led by researchers at OICR, takes a deep dive into how prostate cancer is inherited and points to new opportunities for improved screening, monitoring, treatment and prevention
Prostate cancer is one of the most common cancers in men, but remains one of the most difficult to prevent and a challenge to treat. Some DNA mutations that lead to prostate cancer are inherited yet some collect over a lifetime. Understanding how these mutations interact and contribute to the disease could help patients and their doctors better manage the disease.
In a study, published today in Nature Medicine, Kathleen Houlahan et al. take a deep dive into the inherited factors driving prostate cancer and how these factors affect the course of the disease at a cellular level.
“Prostate cancer is thought to be, in part, an inherited disease,” says Houlahan, first author of the study and a PhD candidate at OICR. “The DNA that a man is born with has an effect on whether he will develop prostate cancer and how aggressive the cancer will be. We set out to uncover how this happens.”
The study investigated the connection between inherited mutations – also known as germline mutations – and a range of important DNA-regulating processes, like DNA methylation.
The associations found in the study, Houlahan says, are a resource that can help bridge our gap in understanding between germline mutations and the mutations that men acquire over their lifetime that eventually lead to prostate cancer.
“When we understand how inherited mutations work, patients with these mutations can be screened and monitored more effectively to ensure the patient is receiving the most appropriate treatment and avoiding unnecessary side effects,” says Houlahan. “We’ve seen this work for patients with mutations in the BRCA genes, but we still need more personalized options for the many men who are living with prostate cancer.”
Since germline mutations can be inherited and are present in nearly all cells in a man’s body, this research demonstrates the possibility of using non-invasive blood-based tests, rather than invasive tumour biopsies, to monitor prostate cancers.
“We could use these findings to help identify a man’s risk of cancer and catch it earlier,” says Houlahan. “Detecting the disease earlier could significantly improve treatment success.”
Houlahan’s study was enabled by data from the Canadian Prostate Cancer Genome Network (CPC-GENE), which have previously been used to find a DNA signature of aggressive prostate cancers and link how a prostate tumour evolves with the severity of the tumour, amongst other significant advancements. CPC-GENE findings serve as a resource for future research and a scaffold on which diagnostic tests and new therapies can be built.
This research was supported in part by OICR, Prostate Cancer Canada, the Terry Fox Research Institute, the Canadian Institutes for Health Research, the Canadian Cancer Society, the Movember Foundation and the National Cancer Institute.
July 30, 2019
Genome Canada, Ontario Institute for Cancer Research and Thermo Fisher Scientific to focus on pancreatic, prostate and breast cancer
CARLSBAD, Calif. – (July 30, 2019) – Genome Canada, the Ontario Institute for Cancer Research (OICR) and Thermo Fisher Scientific are collaborating to develop a complete solution of targeted next generation sequencing (NGS) assays and analysis software designed to more effectively assess – and eventually improve management of – pancreatic, prostate and breast cancer.
The $6 million, three-year initiative aims to standardize advanced molecular profiling in these disease areas and make the assays commercially available globally. Focusing on rapid genomic diagnostics in pancreatic cancer and targeting treatment in breast and prostate cancers, the partnership builds on previous clinical research between OICR and Thermo Fisher and will inform development of three assays that will be utilized to stratify patients in clinical trials in Ontario and other jurisdictions.
“By supporting research and clinical trials, Genome Canada is helping to put more of Ontario’s innovative cancer diagnostics research into clinical use,” said Dr. John Bartlett, program director, diagnostic development at OICR. “This project has the potential to springboard advanced next-generation sequencing to routine clinical use in Ontario and across Canada.”
Breast and prostate cancer are among the most common types of cancer in Canada, and the country’s five-year net survival rate for pancreatic cancer is only 8 percent. However, there is clear evidence that patient outcomes can be improved with NGS-based testing strategies. A recent U.S. health economics study has shown that advanced cancer patients who received treatment based on NGS testing results experienced double the length of progression-free survival without increasing health care costs.1
While some solutions analyze only DNA sequences, the new targeted NGS assays will provide comprehensive genomic profiles by simultaneously assessing DNA and expression signatures from RNA to provide significantly more insight into driver mutations. The OICR/Thermo Fisher team will leverage this advantage by supplementing the new assays with unique DNA/RNA stratification biomarkers – specific to pancreatic, prostate and breast cancer – previously qualified by OICR translational researchers.
The collaboration is partly funded with a grant from Genome Canada through the Genomic Applications Partnership Program (GAPP). Genome Canada will contribute $2 million, the highest possible level of funding support, with the balance split between OICR and Thermo Fisher, which will cover development costs and validation activities.
Previous research collaborations led by OICR and Thermo Fisher are already well on their way to impacting cancer treatment in the future. Of particular note is a 2016 study designed to identify mutations and copy number variation changes in breast cancer, and clinical research utilizing the Oncomine Comprehensive Assay, which also supports both the National Cancer Institute’s Adult and Pediatric MATCH trials in the United States.
“OICR is a leader in clinical research, with extensive clinical trials in progress to improve care for patients with pancreatic, prostate and breast cancer,” said Jeff Smith, global lead of NGS precision medicine initiatives, clinical NGS and oncology for Thermo Fisher Scientific. “When OICR approached our team with the idea for this project, we saw it as another exciting for opportunity to bring Thermo Fisher’s proven Ion Torrent technology to clinical laboratories across Canada and to contribute to future improvement of patient care.”
1 “A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression- Free Survival Without Increased Health Care Costs,” Journal of Oncology Practice, Vol 13, Issue 2, February 2017
May 17, 2019
OICR-supported trial finds new, more sensitive imaging technique can inform treatment decisions and benefit those with recurring prostate cancer
Prostate cancer is the most common type of cancer found in men, but managing the disease is difficult because not all prostate cancers are aggressive and overtreatment can lead to unnecessary side effects, such as hormone imbalances, bowel function issues and erectile dysfunction. After initial treatment, prostate cancer patients are often monitored with a prostate specific antigen (PSA) blood test, but this test provides no information about the location and the extent of the disease. Even with traditional bone scans and CT scans, remnant traces of the disease are difficult to find and often go undetected.
A few years ago, a new, more sensitive type of imaging technique had shown promise in early clinical studies abroad and Dr. Glenn Bauman, Radiation Oncologist at the London Health Sciences Centre, wanted to bring this technique into his practice. He recognized the potential benefits of this method, but didn’t realize how much it could impact the lives of his patients.
Bringing advances to local patients
The new technique, which was originally developed at the John Hopkins Hospital in Baltimore, consisted of a chemical probe, called [18-F]-DCFPyL, which would attach only to prostate cancer cells and light up in positron emission tomography (PET) scans. It can detect very small traces of a tumour that has returned after treatment or spread to a different part of the body.
Bauman teamed up with the co-inventor of [18-F]-DCFPyL, Dr. Martin Pomper, and the Centre for Probe Development and Commercialization (CPDC) to bring this probe to patients in Ontario. CPDC implemented the stringent manufacturing processes needed to create this probe and in March of 2016, Lawson’s researchers were the first to use this technique to scan a patient at St. Joseph’s Hospital in London.
“We teamed up with experts in [18-F]-DCFPyL from the U.S. and experts in prostate PET/CT from Australia to adopt this new technique, benchmark our methods and learn from their experience,” says Bauman. “It’s with collaborations like these that we can accelerate the implementation of new methods to help patients in Ontario.”
Evaluating the benefits for those with prostate cancer
Clinical studies are needed to evaluate the effectiveness new medical techniques in practice. For this technique, Bauman and collaborators needed to test whether it’s improved accuracy and sensitivity could help make better treatment decisions.
“Treatment plans for prostate cancer differ depending on the cancer’s size and location. Whether a cancer returns in the prostate, the pelvic area or elsewhere makes a big difference,” says Bauman. “We needed to test if more sensitive imaging techniques could help patients make better treatment decisions.”
Bauman led the design and development of the Advanced Prostate Imaging of Recurrent Cancer After Radiotherapy (PICs) study to evaluate [18-F]-DCFPyL PET/CT imaging. With OICR’s support over the following two years, PICs enrolled 80 men and scanned them with both traditional imaging methods and with [18-F]-DCFPyL PET/CT.
The study group found that not only can [18-F]-DCFPyL PET/CT detect smaller traces of the disease earlier when it is more manageable, this technique changed treatment recommendations for two in every five patients.
“With this technique, we were able to clarify and reclassify a lot of the traditional scans that were previously uncertain,” says Bauman. “This means that we were able to give prostate-directed treatment with confidence for patients whose cancers reemerged in their prostate and avoid the negative side effects of systemic hormone therapy for these patients.”
Bauman says that the technique also detected double the number of cancers outside of the prostate which were too small to be detected using traditional imaging alone.
Translating clinical findings into practice
Just three years after the first [18-F]-DCFPyL PET/CT scan was taken in Canada, Bauman has embarked on the next stage in translating these findings into routine practice. He and collaborators have teamed up with Cancer Care Ontario to provide access to the [18-F]-DCFPyL PET/CT technique in Toronto, London, Hamilton, Ottawa and Thunder Bay as part of a provincial registry program.
[18-F]-DCFPyL PET/CT can be applied to other challenges that patients and clinicans face with managing prostate cancer, including monitoring how patients respond to treatments. Notably, investigators in Hamilton are investigating how these scans can help predict a patient’s response to treatment in the OICR-supported MISTR trial.
“We have been sufficiently encouraged by our results from the PICs study, through which we have demonstrated the value of this intervention and how it can benefit men with prostate cancer,” says Bauman. “I’m proud to help bring better technologies to our patients in need and enable the adoption of these technologies throughout the province.”
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 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.”
September 20, 2018
Today, OICR’s Dr. Paul Boutros was named the 2018 winner of the Bernard and Francine Dorval Prize. The award is part of the Canadian Cancer Society’s Awards for Excellence in Cancer Research.
September 13, 2018
Sunnybrook researchers develop new magnetic resonance imaging methods to help differentiate between aggressive and non-aggressive prostate cancers
Current needle biopsy techniques have limited accuracy in detecting prostate cancer and determining the tumour’s aggressiveness. New methods are needed to better detect and characterize prostate cancer so that each patient can get the treatment that is most appropriate for them.
May 17, 2018
Dr. Michael Fraser, Director of the Prostate Program in the Computational Biology group at OICR, has been named a 2018 NextGen Star by the American Association for Cancer Research (AACR). Awarded to only eight researchers around the world, AACR’s NextGen Stars program recognizes outstanding early-career scientists who have made significant contributions to cancer research.
April 19, 2018
Largest-ever study of its kind uses a tumour’s past to accurately predict its future
Toronto (April 19, 2018) – Findings from Canadian Prostate Cancer Genome Network (CPC-GENE) researchers and their collaborators, published today in Cell, show that the aggressiveness of an individual prostate cancer can be accurately assessed by looking at how that tumour has evolved. This information can be used to determine what type and how much treatment should be given to each patient, or if any is needed at all.
The researchers analyzed the whole genome sequences of 293 localized prostate cancer tumours, linked to clinical outcome data. These were then further analyzed using machine learning, a type of statistical technique, to infer the evolutionary past of a tumour and to estimate its trajectory. They found that those tumours that had evolved to have multiple types of cancer cells, or subclones, were the most aggressive. Fifty-nine per cent of tumours in the study had this genetic diversity, with 61 per cent of those leading to relapse following standard therapy.
September 25, 2017
Since mitochondria are inherited maternally, it may strike some as an odd place to go looking for connections to prostate cancer. But recently an international research team explored that relationship by looking at how the small amount of DNA contained in mitochondria, a cellular structure, is involved in prostate cancer.