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 19, 2019
Dr. Victoria Hoskin, OMPRN grantee, wins best poster presentation at the 2019 Terry Fox Research Institute Ontario Node Research Symposium for her novel approach to preventing cancer metastasis
The vast majority of cancer-related deaths are caused by cancers that have spread – or metastasized – to other organs. Breast cancer cells, for example, often spread to nearby lymph nodes where they can settle, grow and spread to more distant organ sites, evading surgery and chemotherapy treatment. Dr. Victoria Hoskin has set out to stop these migrating cancer cells in their tracks.
Earlier this year, Hoskin and an interdisciplinary team of researchers at Queen’s Cancer Research Institute (QCRI), found that a specific protein, ezrin, which plays a key function in cancer metastasis, may also have an important immune-modulating role. They went on to find that when ezrin is blocked, the immune system’s T-cells can better recognize, engage and kill the migrating cancer cells in surrounding lymph nodes. As she describes in her recent Oncotarget editorial, these findings may represent a new method to not only prevent cancer metastasis, but to also engage the immune system.
“When we blocked ezrin, we saw that the cancer cells couldn’t migrate and invade into other tissues,” says Hoskin, who is a Postdoctoral Fellow at QCRI. “We’re excited by these findings because they point to a new way to reduce the spread of cancer cells and to potentially boost the immune response against these cancer cells.”
Throughout the course of her research, which was supported in part by the Ontario Molecular Pathology Research Network (OMPRN), Hoskin helped develop a novel experimental animal model that allowed her and her team to track and monitor cancer and immune cells in vivo. The model, she describes, was the critical tool behind her discovery, allowing her to look deeper into the behavior of cancer cells and T-cells within specific organs.
Last week, Hoskin presented her research at the 2019 Terry Fox Research Institute Ontario Node Research Symposium. Among more than 120 other presenters, she won one of three poster presentation awards. Other presentation award recipients included:
- Parasvi Patel, PhD Candidate, University of Toronto and Princess Margaret Cancer Centre
- Noor Shakfa, MSc Candidate, Queen’s University and Queen’s Cancer Research Institute
Hoskin and her collaborators plan to further investigate how T-cells interact with cancer cells in the absence of ezrin.
“What we’ve found is not only scientifically interesting, it could be clinically significant,” says Hoskin. “Metastasis is a serious challenge and our research efforts are dedicated to finding a new solution.”
November 13, 2019
Dr. Brian Keller, an Anatomical Pathology Resident from Ottawa, was one of those recognized for outstanding presentations and innovative research at this year’s Pathology Matters meeting
Through his years of research training, Dr. Brian Keller developed expertise in culturing cancer cells. Under precise conditions in a controlled lab environment, he could take a part of a patient’s tumour and grow it into an experimental model for further research. Keller would study these models to find new treatments for future cancer patients, but he wondered if these models could also help patients today.
While he was an MD/PhD trainee, he received a patient’s sample that was unique. It defied the typical behaviour of a sample and grew remarkably well, faster than normal, exhibiting the cancerous traits that could make it an excellent experimental model.
The sample came from a patient with advanced melanoma whose disease had returned after multiple rounds of treatment. Keller recognized the opportunity to help.
“This patient was in a very difficult situation,” says Keller, who is now an Anatomical Pathology Resident at The Ottawa Hospital. “The standard treatments weren’t working and the patient’s oncologist was thinking of second- and third-line treatment options. Knowing that we had this model in the lab, we thought that we could potentially find a better treatment option if we looked at hundreds of available drugs.”
Keller mobilized the patient’s healthcare team around his idea to find new possible treatment options for the patient. He worked with the patient’s pathologist, medical oncologist, molecular geneticist, laboratory and research technicians, and several other graduate students to grow the tumour sample, analyze its DNA and test approximately 1,200 available drugs on it. Their results aligned with the oncologist’s clinical decision and the patient had an impressive response to treatment, Keller says.
“Every cancer is unique and we’re working towards getting the right treatments to the right patients at the right time,” says Keller. “This represents the direction in which our field is moving. I am hopeful that our generation of clinicians and healthcare providers can help bring more personalized and effective treatment to our patients.”
Keller went on to characterize the patient’s disease and found that it had a unique mutation in the BRAF gene that had never been modeled before. This novel experimental model will continue to serve as a research tool in Dr. John Bell’s lab at the Ottawa Hospital Research Institute, where Keller performed his research, and throughout the global scientific community. The team has made the model available through the American Type Culture Collection’s general repository and a manuscript of the case is under preparation.
“I am fortunate to have had the opportunity to train in Dr. Bell’s lab, where exploration and collaboration are strongly encouraged,” Keller says. “Without exploration, we cannot make discoveries, and without collaboration, we cannot bring our discoveries to our patients.”
Keller presented his findings at the fourth annual Pathology Matters meeting in early October, hosted by the Ontario Molecular Pathology Research Network (OMPRN). His story won him an Outstanding Presentation Award. Other presentation award recipients included:
- Dr. Lina Chen, Anatomical Pathology Resident, Queen’s University
- Christina Ferrone, PhD Candidate, Pathology and Molecular Medicine, Queen’s University
- Chelsea Jackson, PhD Candidate, Pathology and Molecular Medicine, Queen’s University
OICR would like to congratulate award recipients and thank the organizing committee for a successful meeting.
August 12, 2019
OMPRN grantee and former Transformative Pathology Fellow discusses her recently-awarded faculty appointment with the University of Toronto
Despite research advances in identifying the subtypes of kidney cancer, treatment decisions are often based on the size of a patient’s tumour. Dr. Rola Saleeb, who has been studying kidney cancer for nearly a decade, thinks there’s a better way to make these decisions.
“Each month, more than 500 people are diagnosed with kidney cancer in Canada,” says Saleeb. “These individuals and their oncologists face tough decisions to make about their treatment options and I want to help make that decision easier.”
Saleeb, a former OICR Transformative Pathology Fellow and two-time Ontario Molecular Pathology Network (OMPRN) grantee, has recently become a certified pathologist and faculty member in the Department of Laboratory Medicine and Pathobiology at the University of Toronto.
Throughout her doctoral research, Saleeb developed a classification system that could help pathologists distinguish between aggressive kidney cancers and less aggressive cancers. She says this system could, one day, help spare patients from unnecessary surgery if they don’t have aggressive tumours. Additionally, she says classifying these tumours could enable the development of new therapies for these subtypes.
Now as a certified pathologist, Saleeb is the second Transformative Pathology Fellow to have been recruited to a faculty position. Both former fellows have committed to a career where research and development is central to their practice of pathology.
“Not all pathologists do research,” says Saleeb. “But for me, I feel like I can help more patients if I can help find solutions to unsolved problems.”
Saleeb is currently completing a validation study on her classification system. She looks forward to implementing the system at St. Michael’s Hospital and broadening her research to study the molecular origins of kidney cancers and new kidney cancer prevention strategies.
February 12, 2019
Sometimes the simpler, the better: bringing personalized treatment selection for bladder cancer closer to the clinic
Pathology experts review challenges and opportunities in treatment selection for muscle-invasive bladder cancer (MIBC), propose traditional pathology method to achieve same results as molecular profiling at lower cost
Research has shown that some types of bladder cancer respond well to treatment and other types are resistant, yet molecular subtyping, which can help better define a patient’s cancer and direct them to a more targeted treatment, is not performed in the clinic. This means that patients are often treated with a one-size-fits-all approach. Despite recent research progress, the movement of MIBC subtyping to the clinic has stagnated.Continue reading – Sometimes the simpler, the better: bringing personalized treatment selection for bladder cancer closer to the clinic
January 23, 2019
Ontario Molecular Pathology Research Network (OMPRN) helps establish new training standards for pathologists across Canada
Personalized medicine presents a tremendous opportunity for molecular pathologists to contribute to improvements in detecting, diagnosing and selecting treatments for cancer patients. As new diagnostic and prognostic tools continue to emerge, it is becoming increasingly important for pathologists to engage in cancer research and understand new developments across scientific disciplines. Fostering this engagement begins with education.
OMPRN is championing the advancement of molecular pathology training across Canada through its engagement with the Royal College of Physicians and Surgeons of Canada (Royal College), Canada’s governing body for medical education. Together, they are developing a new curriculum for pathology residents based on competencies – the proficiency or ability to perform a skill – rather than the traditional time-based training approach where residents are evaluated based on the amount of time spent acquiring knowledge or practicing a skill.
“The existing competencies around molecular pathology were not adequate in detail, nor were they adequate in rigour,” says Dr. David LeBrun, Principal Investigator at Queen’s Cancer Research Institute and Leader of OMPRN. “So we harnessed the opportunity to improve these training standards for the future of pathology in Canada.”
OMPRN developed a list of molecular pathology competencies, priorities and training strategies to inform a new national curriculum. These suggestions were presented to the Anatomical Pathology Specialty Committee of the Royal College, who accepted several of the proposed strategies and recognized OMPRN’s submission as an official Royal College Curricular Document – a curriculum guide for educators.
One of OMPRN’s major contributions to the new curriculum, which is currently being implemented across Canada, was a competency focused on synthesizing a unified, clinically-actionable report based on results from non-traditional diagnostic tests, such as liquid biopsies or genomic profiling. With this ability, pathologists can better inform clinicians while ensuring that there are no opportunities missed in the detection or diagnosis a patient’s disease.
“With proper training, pathologists can play a key role in bringing the benefits of new research discoveries into the patient experience,” says LeBrun. “These competencies will help ensure that treatment decisions in the clinic are well informed by both conventional pathology techniques and novel tools and resources.”
One of the key challenges of competency-based education is that some training centres may not have the expertise to train their residents on highly-specialized skills. OMPRN is working to address the gap in expertise by developing online education materials to complement the molecular pathology competencies and offering training courses like their inaugural Applied Molecular Pathology Course, which was held January 9-10 in Mississauga.
“Our mission is to create a vibrant community of cancer research-oriented pathologists in Ontario,” says LeBrun. “Through our educational initiatives, OMPRN is helping to build the next generation of pathologists and – in turn – driving the future of cancer innovation.”
For more information on the Ontario Molecular Pathology Research Network, please visit its website.
Learn more about the Royal College’s Competence by Design program in the video below.
September 24, 2018
OICR takes part in international multicentre study to standardize promising breast cancer digital pathology test
The Ki67 immunohistochemistry assay is a test that can help evaluate the aggressiveness of breast tumours, predict disease outcomes, monitor cancer progression and identify patients who are more likely to respond to a given therapy. Despite its potential to help patients with breast cancer, the analysis of Ki67 has not been widely adopted in the clinic, mostly due to the lack of standardization across laboratories.
October 23, 2017
In this post, Monique Johnson shares how the Ontario Molecular Pathology Research Network’s (OMPRN) 2017 Pathology Matters Meeting provided her with new insights into the field and introduced her to Ontario’s molecular pathology community.
September 6, 2017
OICR’s Tissue Portal is a new central entry and exit point for human tissue derived samples handled at OICR. This will serve as a gateway for tissue-based research projects to access over 100 services and resources at OICR being made available through the OICR Collaborative Research Resources on a cost-sharing basis. The Tissue Portal will standardize and streamline the storage, processing and distribution of samples for collaborative research studies at OICR.
June 7, 2017
The Ontario Molecular Pathology Research Network (OMPRN) recently awarded $675,000 of funding to support molecular cancer pathology research in Ontario. The 11 funded projects will involve 22 investigators and seven trainees and address clinically-relevant questions in bladder, brain, breast, endometrial, cervical, renal, pediatric and hematological cancers. The 26 applications that were submitted for review demonstrate the high quality and rich diversity of cancer pathology research in the province. Please visit the Funded Projects page for more information.
OMPRN’s mission is to enhance molecular pathology research capacity across the province by fostering collaboration and cooperation between Ontario academic pathologists, increasing the participation of pathologists in high-quality translational cancer research, and providing opportunities for residents, fellows and early career pathologists to obtain training and mentorship in cancer research. In line with these objectives, all of the research projects funded through OMPRN’s Pathology Translational Research Grants (CPTRG) program are led by pathologists, address questions of clear relevance to cancer care and incorporate important elements of transdisciplinary collaboration and mentorship. Trainees and early career researchers involved in these projects will be supported in their research through attending regular meetings of OICR’s Pathology Club.
The next round of the CPTRG program will be announced in the fall of 2017. Information may be found here: https://ontariomolecularpathology.ca/research-funding
November 23, 2016
On November 16 OICR and the Ontario Molecular Pathology Research Network (OMPRN) joined other organizations around the world celebrating International Pathology Day.
November 16, 2016
Today is International Pathology Day. Around the world and here in Ontario events will be held to raise awareness of the field and its contributions to modern medicine. The work of the Transformative Pathology Program, coupled with the launch of the Ontario Molecular Pathology Research Network (OMPRN), has made for a very successful year thus far for OICR’s efforts in pathology research. Here are some of the highlights. Continue reading – International Pathology Day 2016