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.