OMPRN's Funded Projects

Research Team

Principal investigator: Dr. Sangeetha Kalimuthu

Co-investigator: Dr. Gavin Wilson; Dr. Razan Almohamedi (trainee)

Host institution: University Health Network

Plain – Language Summary: Esophageal adenocarcinoma (EAC) is the leading cause of cancer related deaths in the Western World with limited therapeutic options. Recently, we have developed a classification system that stratifies EAC into three groups based on their microscopic tumour appearance (morphology) and identified molecular expression profiles that are associated with these respective morphological groups. However, this method of molecular profiling is limited in its ability to profile each individual morphological pattern within each group. Furthermore, quantifying these different patterns can be laborious in the everyday clinical setting and limited to expertise of specialist centres. As such, our goal in this study is to develop a deep learning algorithm to predict the individual morphologies within each group using H&E slides from a large cohort of patient specimens and assess the prognostic implication of these. Next, we will use a relatively new technology, Xenium, which will allow us to identify the molecular profile of each individual cell on H&E slides and overlay this with the tumour morphological patterns. Finally, we will train the deep learning algorithm to predict these molecular profiles directly from the H&E slide. This is a first of kind study in EAC, which will permit us to identify new therapeutic vulnerabilities and better stratify patients for existing therapies.

Value to patients and the public: As mentioned, EAC is an aggressive disease that is still poorly understood on a molecular level. As such, this study is a hitherto unexplored method of uncovering the molecular underpinnings of EAC by direct correlation with histomorphological features at single cell resolution with preservation of tissue architecture. Data from this study will facilitate better methods of stratifying patients for existing therapeutic options and identification of further therapeutic targets. The Xenium data will be made public, which will be beneficial to the esophageal and research community. Furthermore, the morpho-molecular correlation will have an impact on the pathology community by providing an opportunity to revise the current pathological classification system to be more prognostically significant.

Research Team

Principal investigator: Dr. George Yousef

Co-investigator: Dr. Rob Hamilton; Dr. Jane Bayani; Dr. Ioannis Prassas, Dr. Youssef Youssef (trainee)

Host institution: University Health Network

Plain – Language Summary: Testicular cancer is the most common cancer in young men, and seminoma is its most frequent type1. Most men with seminoma are cured after surgery removing the testicle (orchiectomy), but about 1 in 5 will later experience a relapse. Unfortunately, doctors cannot reliably predict at diagnosis who will relapse. Currently, factors such as tumor size or the presence of tumor cells in blood vessels are not very accurate, which means that some men receive potentially harmful and unnecessary additional treatment while others are under-treated.

Our project will explore improved ways to predict which patients are at risk for relapse. We are using digital pathology, where ML-based image processing algorithms analyze microscope images of tumor tissue to find patterns that pathologists cannot see with the naked eye. Early work shows this approach can identify subtle features linked to relapse, but the results are often without biological explanation, something that limits translation of this knowledge.

To make these tools more useful and trustworthy, we will combine digital pathology with spatial omics with the goal of uncovering the hidden biology that drives drives prognostication. For example, if digital pathology highlights a in the tissue, spatial omics can reveal whether this area shows any signs of immune evasion, low oxygen, or aggressive growth.

By combining these approaches, our team hopes to create more accurate and biologically meaningful tools to guide care for seminoma patients and improve their quality of life.

Value to patients and the public: Seminoma tumors affects young men often during their most productive years of life. While the majority are cured with surgery, about 20% will relapse and require additional therapy. Because current tools cannot accurately predict relapse, many patients face difficult choices: undergo unnecessary adjuvant treatment and risk long-term toxicities, or remain on surveillance with the anxiety of possible relapse. Both pathways carry significant emotional, physical, and financial burdens to the patient.

This project directly addresses this gap by developing new tools that combine AI and computational pathology with cutting-edge molecular profiling of tissue (spatial omics). This integration has the potential to deliver more accurate and biologically meaningful predictors of relapse at the time of diagnosis. For patients, this means improved information and more confidence in decision-making, leading to personalized treatment strategies that avoid both over-treatment and under-treatment.

Additionally, our novel proposed work is expected to unlock new biology and generate novel biological insights into seminoma progression, potentially leading to the discovery of novel therapeutic targets/biomarkers that could benefit future patients.

Importantly, this project is at its core a truly collaborative framework and includes strong training and mentorship components, promoting interdisciplinary training of clinician-scientists and AI experts.

Research Team

Principal investigator: Dr. ​​Roman Zyla​​

Co-investigator: Dr. ​​Harriet Feilotter; Dr. Peter Yousef (trainee)

Host institution: Mount Sinai Hospital​​, Pathology and Laboratory Medicine Department

Plain – Language Summary: ​​​HGSC is an aggressive form of ovarian cancer. Some HGSCs are characterized by a defect in the homologous recombination pathway of DNA repair. This defect makes them sensitive to treatment with a class of targeted drugs called PARP inhibitors. It is critical to identify which HGSCs have HR deficiency in order to identify which patients should be offered treatment with PARP inhibitors. Currently, there are molecular tests which are used to detect HR deficiency, however they are not widely accessible and are often expensive and time-consuming to perform. This can delay access to therapy for patients. It is known that HGSCs with HRD have slightly different microscopic features to those without HR deficiency. We hypothesize that these differences can be reliably identified by an artificial intelligence algorithm trained on histologic slides from HGSCs. Such an algorithm would allow for tumours to be quickly pre-screened for the likelihood of HRD, and those tumours which are likely to be HRD can be prioritized for confirmatory molecular testing. ​​

Value to patients and the public: PARP inhibitor therapy for HGSCs represents a breakthrough in targeted treatment of these aggressive tumours. They are particularly effective in tumours with HRD, and therefore timely and accurate HRD testing is critical to ensure patients are offered the correct therapy. Currently available molecular assays for HRD testing are highly accurate but are often time-consuming to run and few labs possess the technical capabilities to offer them. Often, clinicians must send tumour tissue to commercial laboratories for testing, which introduces delays in turnaround time and expense to patients (in the case of unfunded tests). By exploiting the morphologic differences between HR-deficient and HR-proficient HGSCs, an AI algorithm capable of classifying tumour HRD status through examination of histologic slides alone would represent a fast and inexpensive adjunct to traditional molecular methods. This would enable clinicians to prioritize cases likely to harbour HR-deficiency for confirmatory testing, and a subset of cases could potentially be ‘screened out’ from requiring any molecular testing, thereby reducing turnaround times as well as costs to the healthcare system and patients. Additionally, while the goal of this algorithm would not be to completely replace molecular-based HRD testing, it could serve as a primary testing method in low- and middle-income jurisdictions which otherwise have no access to advanced molecular laboratory infrastructure, opening new avenues for access to targeted cancer therapy in these countries.

Research Team

Principal investigator: Dr. Qi Zhang

Co-investigator: Dr. Shawn S. C. Li; Dr. Jacob Houpt (trainee)

Host institution: London Health Sciences Centre Research Institute

Plain – Language Summary: Some breast cancer cells can travel to the brain and grow into new tumors, which is called brain metastasis. Once cancer spreads to the brain, treatment options are limited, and the prognosis is dismal. Right now, doctors have no reliable way to predict which breast cancer patients are at higher risk of developing brain metastasis. This means many patients are diagnosed too late, when the cancer has already spread to the brain.

In our previous research, we discovered a molecule called PTK7 that is much more common in brain metastases than in breast tumors that do not spread to the brain. PTK7 appears to help cancer cells survive in the brain and grow in areas filled with scar-like tissue with fewer immune cells. We believe PTK7 could be used as a predictive marker to help doctors identify which breast tumors are more likely to spread to the brain.

In this new project, we will study PTK7 in a new group of breast cancer samples, including both tumors in the primary site (breast) and brain metastases. We will use advanced lab techniques and computer-based image analysis to measure PTK7 levels and see how it relates to the surrounding tissue environment. We will also build a scoring system that could be used by pathologists to identify patients with high-risk of brain metastasis. Our long-term goal is to develop a test that helps doctors detect tumors with worse prognosis
earlier, allowing for more personalized care and better outcomes.​​

Value to patients and the public: Brain metastases are one of the most life-altering and deadly complications of breast cancer. They often occur without warning and are typically diagnosed late, when treatment options are limited and less effective. For patients and their families, the diagnosis of brain metastasis brings immense emotional, cognitive, and physical challenges. Despite this, there are currently no tools used in routine care to identify which breast cancer patients are at higher risk of brain metastasis.

This project aims to fill that critical gap by validating a new biomarker, PTK7, which we discovered to be strongly associated with brain metastases. If successful, this research could lead to a laboratory test that helps oncologists and pathologists identify patients who are more likely to develop brain metastasis, before it happens. With earlier identification, patients could benefit from more frequent brain imaging, closer monitoring, and potentially earlier or preventive interventions.

In addition to improving diagnosis, this work explores how tumor cells interact with their surrounding environment in the brain. Understanding this interaction could lead to new treatments that target not just the cancer cells, but also the supportive environment they rely on to grow.

Importantly, a patient partner will be involved throughout the project, ensuring that our questions, methods, and communication strategies reflect the priorities and needs of people living with breast cancer. This partnership will help ensure that our research leads to real-world benefits for patients, caregivers, and the broader community.

Research Team

Principal investigator: Dr. Marcio Gomes

Host institution: University of Ottawa

Plain – Language Summary: Molecular pathology is a branch of medicine that focuses on understanding diseases at a molecular level, particularly by examining genes and other molecules in our cells. This field has become incredibly important in diagnosing and treating diseases like cancer. However, many practicing pathologists (doctors who study tissues and diagnose diseases) were trained before these new techniques became common, so they didn’t learn about molecular pathology during their education.

In the past, only a few specialists, like those with advanced training in genomics (the study of genes), handled these complex cases. But now, with the rise of new technologies like next-generation sequencing (NGS), the number of tests and biomarkers (molecules that indicate the presence of a disease) has skyrocketed. This has created a big challenge: there aren’t enough genomics-trained specialists to manage all the cases, and regular pathologists need to learn how to handle simpler ones.

The problem is that the current training programs in molecular pathology are very detailed and go beyond what most practicing pathologists and pathology residents need to know. Our project aims to create a more practical and focused training program that teaches the specific skills these doctors need to perform basic molecular tests. We will follow a structured approach to design this program, ensuring it meets the real-world needs of pathologists. This new curriculum will include educational materials, assessments, and workshops to help pathologists and residents better understand and use molecular diagnostics in their daily work..

Research Team

Principal investigator: Dr. Daniel Xia

Co-investigator: Dr. Tracy Stockley

Host institution: University Health Network

Plain – Language Summary: DNA methylation refers to a type of chemical changes on the DNA molecule that affects how genetic information is interpreted and utilized. Since tissues in the body have different methylation patterns, these patterns can be used to identify where cancers originated from (e. g. , lung versus stomach). In tissue samples, methylation analyses have been used to assist in challenging cancer diagnoses. In blood samples, methylation patterns on fragments of circulating DNA from dying cancer cells could be used for early screening of cancers, and to monitor progress after treatment. To date, researchers in this area have mostly used comprehensive methods, for example, those involving the quantification of methylation levels at hundreds of thousands of different sites, to achieve desired results. While technically successful, these methods could prove too complex and expensive for routine clinical use. In a previously funded CPTRG project, we proposed that DNA methylation testing could be greatly simplified by reducing the number of methylation sites evaluated. As proof-of-principle, we developed a diagnostic test for the droplet digital PCR platform, which is comparatively simple and widely-available, to distinguish gastric from pancreatic cancers using information from only a single methylation site. For this Stream 4 application, we propose extend this “minimalist” approach to lung cancers by developing simple tests for routine pathology specimens and to look for lung cancer-specific signatures in the blood.

The technical work will take place at the Advanced Molecular Diagnostics Laboratory at the University Health Network, which specializes in this type of translational research and in test implementation.

Research Team

Principal investigator: Dr. Rola Saleeb

Co-investigator: Dr. Georg Bjarnason

Host institution: St. Michael’s Hospital

Plain – Language Summary: Each month, more than 500 people are diagnosed with kidney cancer in Canada and it is estimated that 1 in 4 would die of the disease. However, not all kidney cancers behave the same. Currently tumor aggressive potential is assessed solely on how it looks under the microscope. That system is limited though and does not always accurately predict the tumor behavior and its response to therapies. In this study we assess a new combined morphological and biological/genomic system to better predict kidney cancer behavior.

The new system has great potential to enhance kidney cancer patient care.

Research Team

Principal investigator: Dr. Michael Rauh

Co-investigator: Dr. Sagi Abelson

Host institution: Queens University

Plain – Language Summary: The incidence of blood system cancers, such as myelodysplastic syndrome, acute myeloid leukemia (AML), and non-Hodgkin lymphoma are expected to increase with our aging Canadian population. Outcomes are especially dismal in older patients and new approaches to diagnosis and treatment are needed. Our group has pioneered discoveries of the earliest, pre-cancerous stage of blood cancers, known as clonal hematopoiesis (CH). We have shown CH can be detected up to 10 years in advance of AML, when patients have no signs or symptoms, using a simple genetic blood test. We have shown CH cells increase inflammation and organ damage throughout the body, contributing to other diseases of aging, like heart and lung disease. Targeting this pre-cancerous CH phase may contribute to healthy aging, and present a radical new prevention strategy for AML and other blood cancers. Here we will develop more sensitive genetic tests to detect CH, and better understand the lifestyle and environmental factors that contribute to blood cancer progression and inflammatory diseases. We will study cancer development over time in matched samples3 from patients who were healthy when they enrolled in a large Canadian population study and later presented to hospitals with blood cancers. Our work will facilitate the application of our novel tests to the most at-risk populations, including forging new relationships between hospital-based hematopathologists and primary care providers. Our proposal will set the stage for more standardized workup and earlier detection of blood cancers, and potentially novel blood cancer prevention trials.

Research Team

Principal investigator: Dr. Sangeetha Kalimuthu

Co-investigator: Dr. Jonathan Yeung

Host institution: University of Toronto

Plain – Language Summary: Histological examination remains the gold standard in characterising and grading EAC tumour tissue, where EACs can be broadly divided into two types, (intestinal/diffuse) based on their ability to form glandular elements. Recently, we have observed an additional morphological pattern resembling NE tumours. However, the molecular makeup and therapeutic implications of these different patterns have not been explored. Moreover, the utility of patient derived organoids to model and characterize these features are unknown. Our goal in this study is to better understand the mechanism of development and prognostic significance of these different morphological patterns, which would permit us to better predict the course of disease development in patients and identify potential therapeutic vulnerabilities.

Research Team

Principal investigator: Dr. Hong Chang

Co-investigator: Dr. Dennis Kim

Host institution: Princess Margaret Cancer Centre

Plain – Language Summary: The Philadelphia chromosome is an abnormal chromosome which forms when chromosome 9 and chromosome 22 break and exchange portions. Ph is associated with almost all CML cases and many ALL cases, but in rare instances, in AML patients. Ph+ AML accounts for 0.5 to 3 percent of all AML cases, and the outcome is generally poor in these patients, with a median survival of 9 months. The pathophysiology and pathogenesis are largely unknown due to the nature of its rarity and lack of comprehensive genomic analyses. We have identified 9 Ph+ AML cases from our AML patient cohort. We will conduct a single cell sorting technique and a comprehensive cellwide profiling to demystify the cellular structure and clonal origin of this disease. Thus, we will be able to determine the best approaches to treatment and improve the survival outcomes of Ph+ AML.

Research Team

Principal investigator: Dr. Qi Zhang

Co-investigator: Dr. Parisa Shooshtari, Dr. Shawn Li

Host institution: Western University

Plain – Language Summary: Cancer from other parts of the body can spread to the brain. This is known as brain metastasis. Breast cancer is one of the most common cancers that spreads to the brain. Most breast cancer patients with brain metastasis are diagnosed quite late and with serious complications. Unfortunately, our overall understanding of the brain metastasis process is superficial, thus limiting our ability of early diagnosis and treatment. In our study, we will examine samples from breast cancer patients to identify changes in their cancer cells that allow the cells to spread and evade brain defense mechanisms. We will use cutting edge techniques known as NanoString Digital Spatial Profiling and mass spectrometry to identify the changes responsible for allowing cancer cells to flourish in the brain microenvironment. We hope that our work can identify key changes in that may serve as targets for the future treatment of breast cancer brain metastasis.

Research Team

Principal investigator: Dr. Michelle Downes

Co-investigator: Dr. Thomas Kislinger

Host institution: Sunnybrook Research Institute

Plain – Language Summary: Prostate cancer is the most common non-skin cancer in men in North America. Some men have very aggressive cancers and require intensive therapy which can carry significant side effects. Determining who should receive maximal therapy vs. those that need less treatment is a challenge in the management of prostate cancer. Certain features of prostate cancer are now known to be associated with higher risk of cancer spread and recurrence. These features can be seen in tissue samples and are called “morphologic biomarkers”. In particular, cancers that grow in a sieve-like fashion or as solid sheets or single cells are recognized as being almost inevitable in patients whose cancers spread to their lymph nodes. These features cause concern for surgeons and oncologists who will tend to intensify treatment if they are present. However, not every patient with these findings will have cancer spread but may develop debilitating side effects from treatment. The goal of this project is to investigate the genes and proteins in these high-risk cancer patterns and determine how they associate with spread in3 the lymph nodes. Existing patient tissue samples with and without cancer spread to the nodes will be assessed to compare and contrast the gene and protein patterns. We think this will allow us to identify new markers that can be used to assess tissue samples so as to identify the amount of treatment a patient will require to individually manage their cancer.

Research Team

Principal investigator: Dr. Matthew Cecchini

Co-investigator: Dr. Aaron Ward

Host institution: Western University

Plain – Language Summary: Lung cancer is the most deadly cancer affecting Canadians and is responsible for on average 58 deaths every day. Recent advances in therapies have resulted in a significant improvement in survival for patients. One of the most promising therapies for many patients is immunotherapy, which works by activating the bodys own immune system to destroy the tumour cells. The problem is finding out which patients will benefit from these therapies. The rationale for this study is to find a better way to predict which patients will respond to immunotherapy. Currently, pathologists utilize a test that determines how many tumour cells express a protein known as PD-L1. In general tumours with high levels of PD-L1 are treated with immunotherapy alone and tumours with low levels or no PD-L1 require treatment with typical chemotherapy. There is another test known as tumour mutational burden (TMB) that counts the number of mutations in a patients tumour. The most accurate way to predict the response of tumours to immunotherapy is by combining both PD-L1 status and tumour mutational burden. However, TMB is challenging to perform, expensive and not routinely completed in Canada. This project seeks to validate an artificial intelligence test that can predict tumour mutational burden from the digital image of the tumour. If successful this test would provide a fast, accurate and effective means to improve our ability to predict response to immunotherapy at the time of diagnosis and help ensure that all patients with lung cancer receive the most effective therapies.

Research Team

Principal investigator: Dr. Hubert Tsui

Co-investigator: Dr. Arun Seth

Host institution: Western University

Plain – Language Summary: The diagnosis and treatment of blood cancers often starts with laboratory testing of blood or bone marrow. The latter is the blood making factory and can provide important information in a liquid form (the aspirate) and a solid form (the biopsy). Bone marrow biopsies have the benefit of preserving the structural relationship of different types of blood and their supporting cells and sometimes this is the only material available when an aspirate cannot be obtained. This situation often happens when the cancer burden is very high or the bone marrow is scarred. Studying bone marrow biopsies and eventually using geographical information for clinical purposes is important because how cancer cells grow in relation to other normal cells in their proximity is known to affect how cancer cells respond or resist therapies. Unfortunately, innovative methods for diagnosis, prognosis, treatment and research are limited in bone marrow biopsies by the bone softening procedure which renders genetic material depleted and damaged. In this proposal, we have deployed a gentler way of softening bone that potentially better preserves material for genomic clinical tests and translational research without affecting morphology assessments needed for routine clinical care. We propose to demonstrate the improved molecular assays by performing a variety of clinical and research genetic tests on bone marrow biopsies from various blood cancers including a subset where liquid bone marrow aspirates are especially limited by a cancer-induced scar forming process called myelofibrosis.

Research Team

Principal investigator: Dr. Anjelica Hodgson

Co-investigator: Dr. Thomas Kislinger

Host institution: University of Toronto

Plain – Language Summary: Adenocarcinomas of the endocervix, the canal which connects to outer cervix to the main part of the uterus, are tumours that are mostly caused by infection with high risk human papillomavirus infection. If possible, these tumours are treated by removing them, and pathologists are the doctors that examine them. At times, pathologists struggle with how to classify these tumours but, there have been recent developments in how a) the type of tumour (tumour subtype) is recognized and b) how aggressive the tumour looks (pattern of invasion). These recent developments are supported by different types of previous studies however, our goal in performing this study is to leverage a modern type of analysis (proteomics) to provide a novel type of information that will strengthen the appeal of these useful developments, by providing underlying biological evidence.

Research Team

Principal investigator: Dr. Klaudia Nowak

Co-investigator: Dr. Kieran Campbell

Host institution: University of Toronto

Plain – Language Summary: Lymphocytes are cells present within the human body that help respond to infections. Recent studies have demonstrated the presence of lymphocytes and tertiary lymphoid organs (TLOs- aggregates of different types of lymphocytes) near or in between cancer cells can help predict better outcomes in patient survival. Here, we will examine TLOs in the setting of pancreatic ductal adenocarcinomas (PDACs). PDACs represent approximately 90% of all pancreatic cancers and are often characterized by their aggressive nature and exceptionally poor patient survival. While TLOs in the setting of PDACs have been associated with better prognostic outcomes, whether this is predictive across all patient stages and whether there is further variation in TLO types that would better predict patient outcomes remains unknown. Here, we plan to count TLOs in a large PDAC patient cohort and use a cutting-edge spatial technology called Nanostring DSP that will measure the expression of genes in both TLOs and tumour cells in a pilot cohort. Together, this will allow us to associate TLO status with patient outcomes across all stages of disease. This will further allow us to measure the gene expression patterns of each TLO and enable us to discern whether there are multiple subtypes of TLOs in patients and how they interact with the nearby tumour. We will then be able to re-score the large cohort of patients for these TLO subtypes and ascertain how predictive they are of patient outcomes. Together, this study will be the first to help answer long standing questions in how TLOs relate to the survival of patients with pancreatic cancer.

Research Team

Principal investigator: Dr. Qi Zhang

Co-investigator: Dr. Charles Ling

Host institution: Western University

Plain – Language Summary: Polyps in large bowel are very common, affecting 1 in 4 people in general and 1 in 2 people in those older than 50 years. Most of them are harmless. However, a small proportion of them contain cancer. Colon cancer is the third most common cancer in North America. The diagnosis of malignancy in a polyp is made by pathologists identifying cancer cells in the deep layer of the bowel wall under the microscope: a process known as invasion. However, non-cancer cells can be misplaced in the same location which can mislead the pathologists to make the wrong diagnosis. Although there are a few features pathologists use to tell apart “true” and “pseudo” invasion, this is never an easy task. Often times a panel of expert pathologists cannot reach agreement. With the advanced technology in image analysis and machine learning, the artificial intelligence sometimes outperforms human’s eyes in imaging pattern recognition. We identified 100 cases of colorectal polyps with cancer (true invasion) and 100 cases of colorectal polyps with features mimicking cancer (pseudo-invasion), diagnosed with consensus by a panel of expert pathologists specialized in this field. We will develop a machine learning algorithm that can recognize cancer and its mimics using high resolution whole slide images of those cases. We will compare the diagnostic accuracy of the algorithm with pathologists. After the algorithm is fully validated, we will build a web application and publish it online to allow access by pathologists worldwide. Our ultimate goal is to aid pathologists in making an accurate diagnosis of colon cancer.

Research Team

Principal investigator: Dr. Sonal Varma

Co-investigator: Dr. Konstantinos Plataniotis

Host institution: QueensUniversity

Plain – Language Summary: Colorectal cancer (CRC) is 2nd most common cancer in Ontario. It has been shown that individuals at risk of developing CRC form small polyps in the colon that can then progress to become cancerous. Therefore, CRC surveillance is performed by various methods including colonoscopy in people over 50 years of age to identify and remove these polyps. The polyps removed during surveillance colonoscopy forms the bulk of workload of gastrointestinal pathologists, even though the diagnosis in majority of the cases is quite straight-forward. This will continue to increase with increasing age of the population. Hence, we are proposing an automated process to screen these polyps using artificial intelligence (AI) techniques. AI algorithms will be trained to screen and classify these polyps with high accuracy. Any polyps that can not be classified with confidence will be flagged for pathologist review, thus reducing the workload and allowing more time to devote to complex cases. AI will also serve as a ‘second reader’ to alert the pathologist to any discrepancy and as quality indicator.

Research Team

Principal investigator: Dr. Larissa Liontos

Co-investigator: Dr. Anne Martel

Host institution: Sunnybrook Health Sciences Centre

Plain – Language Summary: AML and MDS are rare blood cell cancers that become more common in older individuals, individuals exposed to carcinogens and in individuals with some inherited gene mutations. From many prior research studies, several gene mutations have been identified that contribute to the development and progression of AML and MDS. One important gene, P53, is involved in the repair of DNA damage and maintains the integrity of DNA. When p53 is lost or mutated, genetic “instability” ensues resulting in multiple gene mutations. Genetic instability allows the disease to progress despite our best efforts to treat it. Newer treatments are becoming available that may improve outcomes for such patients therefore knowing the P53 status at the time of diagnosis is critical in deciding on which treatment to choose. To identify a P53 mutation, DNA from bone marrow can be sequenced, however, this process is time-consuming and the result takes 3-4 weeks to be available. Staining for the P53 protein in the bone marrow biopsy may be another way to determine whether a mutation is present, however, the interpretation of protein staining in biopsies is subjective and depends on the pathologist looking at the tissue. Digital imaging is becoming more widespread in pathology and the development of computer algorithms to analyze biopsy samples may be a method that reduces the subjectivity in the interpretation of stains. In this project we propose to use digital imaging analysis of AML and MDS cases to determine whether P53 mutation status can be predicted.

Research Team

Principal investigator: Dr. Phedias Diamandis

Co-investigator: Dr. Stephanie Lheureux

Host institution: University of Toronto

Plain – Language Summary: Ovarian cancer is an aggressive cancer of the female reproductive system that is most commonly diagnosed at advanced stage where only 30% of patients survive more than 5 years from diagnosis12. Despite spirited surgical and medical therapy, this poor outlook has remained fairly unchanged despite many breakthroughs in our understanding of cancer biology13. One recent explanation for these previous failures is that while we often think of a patient’s tumor as being a homogenous mass of identical cancer cells, there are in fact a number of tumor sub-clones within each cancer that respond differently to our conventional and traditional therapies10. This means that existing treatments may not equally target all tumor cells and allow resistant subclones to survive and drive disease recurrence and progression. To address this, this collaborative team plans to harness expertise in artificial intelligence and unique clinical cohorts to explore if this technology can help automate the detection of biologically distinct tumor subregions and understand the biological significance of these computer defined regions. First, they will assess if computer defined regions of variability do indeed show unique biological activity that may be driving partial responses to therapy. Secondly, they will examine if the degree of morphologic variation within these cancers can predict response to existing therapies. Routine detection and characterization of tumor subclones, within each individual patients’ tumor, could help propose personalized and effective drug combinations that together target a larger fraction of the overall tumor biology. This could ultimately provide more durable responses for patients.

Research Team

Principal investigator: Dr. Daniel Xia

Co-investigator: Dr. Peter Sabatini, Dr. Tracy Stockley

Host institution: University of Toronto

Plain – Language Summary: Small B-cell lymphomas (SBCLs) are common cancers that arise from cells of the immune system.  In order to determine the optimal management for each lymphoma, doctors must first assign it to a specific category, that is, classify or diagnose the disease.  While traditional approaches for lymphoma diagnosis are very good, there remain significant numbers of cases that cannot be easily categorized.  To address this, we plan to evaluate the diagnostic benefit of molecular technologies based on DNA methylation.  Methylation markers on DNA act as “on” and “off” switches for the programming of unique cell types; as such, methylation signatures are useful for pinpointing the origins of cancers, thereby assisting with disease categorization.  In this study, we will evaluate two complementary approaches of DNA methylation testing of SBCLs.  The first is methylation profiling, which determines the statuses of hundreds of thousands of methylation markers in each cancer in a comprehensive fashion.  The second is “minimalist” approaches to methylation testing, unique to our study.  To explain, in the minimalist approach, we use data analysis reduce the number of methylation markers needed for accurate diagnosis in order to create less expensive and easier-to-implement tests for laboratories.  As a multi-disciplinary collaboration, the overall goal is to generate new molecular tools to improve SBCL diagnostics.

Research Team

Principal investigator: Dr. Phillip Williams

Co-investigator: Dr. Irene Andrulis

Host institution: Mount Sinai Hospital

Plain – Language Summary: Breast cancer is the most common cancer in women. Breast cancer can occur by chance (sporadic), or by genetic mutations (familial). The most common genes that cause familial breast cancer are BRCA1 and BRCA2. Cancers caused by mutations in these genes can be associated with distinct patterns of tumour cells and immune cells that interact with the tumour cells. Some of these immune cells are associated with a good prognosis in sporadic breast cancer when present, and some have been targeted by specific drugs. Little is currently known about these immune cells and their surrounding environment in familial breast cancers. This study aims to look at the immune cells in familial breast cancers and breast cancers that share features with familial cancers. This is done by determining which immune cells are present by labelling those cells with specific markers using immunohistochemistry techniques. This can be time consuming and requires multiple tissue samples. A novel alternative to this method uses a mass spectrometer, which can evaluate many markers at the same time, conserving tissue. This technique is very new and has not been used to evaluate familial breast cancers before. The two techniques will be used to identify the immune profile of breast cancers, to see which types may be associated with prognosis, and, at the same time, identifying a potential target(s) for future drug therapy.

Research Team

Principal investigator: Dr. Shamini Selvarajah

Co-investigator: Dr. Theodorus Van Der Kwast

Host institution: University of Toronto

Plain – Language Summary: Bladder cancer (BC) is one of the leading causes of cancer-related deaths worldwide. At diagnosis, most BC are confined to the inner lining of the bladder, and known as Non-Muscle Invasive BC (NMIBC). While most of these can be treated conservatively, a subset of these are inherently aggressive and will recur frequently and/or progress to the Muscle Invasive (MIBC) form. Given the variability in clinical behaviour, it is critically important to be able to identify which NMIBC are more aggressive cancers, so that they can be steered towards alternative treatment options. The tools available at present to predict aggressive behaviour are based on morphologic and clinical features, and are not very accurate, requiring patients to have to have life-long surveillance to look for tumour recurrence. An alternative approach exists, already validated in other cancer types, in which the changes at the molecular level are explored for features known as “biomarkers” of aggressiveness. In this study, we are specifically interested in two biology processes that are linked to aggressive tumour behaviour, which include epithelial-to-mesenchymal transition and tumour immune resistance. By profiling the status of the genes in these processes in NMIBC exhibiting aggressive behaviour with those that did not, we will derive a molecular signature that heralds an aggressive disease course. Such a signature can be an important clinical tool in the future to guide the therapy of BC according to the level of risk of invasiveness.

Research Team

Principal investigator: Dr. Neil Renwick

Co-investigator: Dr. Katharin Tyryshkin

Host institution: Queens University

Plain – Language Summary: Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive cancer. Standard chemotherapy treatment is generally effective and most patients are cured. However, in approximately 40% of DLBCL patients, the disease either fails to respond to treatment or relapses later; patients with such “refractory” or relapse disease are at high risk of dying. Being able to predict the response to therapy from biopsied tumor tissues at the time of diagnosis would allow faster and more direct access to experimental therapies that could dramatically help these patients. microRNAs (miRNAs) are genetic control molecules that are present in all human cells including cancer cells. Some miRNAs are also excellent disease markers because they are only found in one disease type or stage. We believe that miRNAs can be used to distinguish patients who will do well with standard therapy from those who will have a poor outcome. In this proposal, we will combine their expertise in medical oncology, lymph node pathology, miRNA diagnostics, and computer science to identify miRNAs that predict treatment response. The project has a single aim: to assess the clinical utility of miRNAs in DLBCL classification and prediction of treatment response. Successful completion of this proposal will establish a simple test to inform treatment decisions and improve the clinical outcomes of a sizeable set of DLBCL patients.

Research Team

Principal investigator: Dr. Marcio Gomes

Co-investigator: Dr. Bryan Lo

Host institution: University of Ottawa

Plain – Language Summary: In patients with multiple lung cancers, staging is guided by whether the tumours are thought to have arisen separately (multiple primary tumours; MPT), or if they are a result of spread within the lung (intrapulmonary metastasis), which confers poorer prognosis. The traditional routes of metastasis involve tumour cells travelling through the bloodstream or lymphatics (vascular/lymphatic intrapulmonary metastasis; VIM). However, the lung is composed of interconnected airway spaces that can potentially carry tumour cells to distant parts of the lung — a concept known as aerogenous intrapulmonary metastasis (AIM). Although the existence of AIM has been suggested by some researchers, it has not been confirmed by molecular studies, and is likely under-recognized and misclassified as MPT in practice. Our group has previously proposed a set of clinical, radiologic and pathologic criteria that can distinguish cases of AIM from VIM and MPT. In this study, we will examine cases of patients with multiple resected lung cancers that meet these criteria for AIM, VIM or MPT. We will analyze the genetic and molecular signatures in these tumours, which will enable us to determine whether paired tumours correspond to clonal neoplasms (intrapulmonary metastasis) or non-clonal neoplasms (multiple primary tumors). This will serve to confirm the existence of AIM, validate criteria in distinguishing AIM from VIM and MPT, and identify gene mutations associated with AIM that could be targeted in precision medicine treatments. Overall, our study will be the first to prove the concept of AIM and will help to understand its clinical significance.

Research Team

Principal investigator: Dr. Bojana Djordjevic

Co-investigator: Dr. Arun Seth

Host institution: Sunnybrook Health Sciences Centre

Plain – Language Summary: Treatment of endometrial (womb) cancers includes surgery (removal of the womb) or hormonal treatment, depending on the degree of severity and spread of disease. There is a growing interest in hormonal treatment for patients wishing to have children or patients that have other medical conditions that prevent them from having surgery. Hormonal treatment includes progesterone based therapy, which is currently reserved for precursor lesions and early low grade endometrial cancer (grade 1). Moreover, some women with cancers of intermediate grade (grade 2) are also interested in hormonal treatment in order to delay surgery and allow time for a successful pregnancy. However, not all cases respond to hormonal treatment or some tumors recur after treatment. A current challenge in management of these cases is to identify patients who would respond to hormonal treatment and for whom surgery can be safely delayed. Our aim is to recruit intermediate grade cancer patients awaiting surgery at the Sunnybrook gynecological cancer clinic to receive a 4-week hormonal treatment preoperatively and correlate therapy response with clinical information, microscopic tumor appearance and their molecular make-up. Based on our previous studies, we believe that a proportion of these intermediate grade cancers will successfully respond to treatment with progesterone. Through the currently proposed study we hope to be able to identify markers that would identify which patients would benefit from hormonal treatment and hence allow physicians to personalize their treatment.

Research Team

Principal investigator: Dr. David Berman

Co-investigator: Dr. Robert Siemens, Dr. Amber Simpson

Host institution: Queens University

Plain – Language Summary: In many fields, expert operators use precise quantitative measurements to guide decision making. Surprisingly, such measurements are rarely used by pathologists when they evaluate cancers and gauge their potential to invade and spread. By analogy to aviation, pathologists are stuck in the era before altimeters and air speed instruments, flying by sight alone. As a case in point, in early bladder cancer, cancer grade is an assessment by a pathologist of the shapes and arrangement of cancer cells. Cancer grade is the primary predictor of aggressive behavior. Current bladder cancer grading does not use any quantitative criteria. Its subjectivity and lack of reliability limit its utility in research and clinical practice. The advent of sophisticated image analysis programs and informatics techniques make it feasible to measure the size, shape, and arrangement of cancer cells, and to derive better evidence-based rules for grading. This project will use such techniques to better define objective grading criteria and ensure that they provide clinically useful information regarding the risk that a patient’s cancer will cause harm in the future. The result will not only improve decisions around monitoring and therapy, but also empower better research into the molecular events that drive aggressive behavior. Finally, by better defining rules for grading, this work will enable more effective and efficient training and more consistent practice by pathologists worldwide.

Research Team

Principal investigator: Dr. Harman Sekhon

Co-investigator: Dr. Bryan Lo, Dr. Trevor Flood

Host institution: The Ottawa Hospital

Plain – Language Summary: Penile squamous cell carcinoma (PSCC) is a type of malignant cancer that occurs predominantly in elderly men. Fifty percent of cases are associated with infection of human papillomavirus (HPV). Localized PSCC is treated by surgery, which includes total or partial resection of the penis to remove and control the spread of tumour. These procedures have obvious physical and psychological implications for the patient. Furthermore, PSCC tumours that have metastasized are difficult to treat and are typically resistant to conventional chemotherapy and radiotherapy approaches. It is clear that alternative treatment modalities are needed. Precision medicine is a promising therapeutic strategy that is changing the way we treat cancer. Precision medicine uses a patient’s own genomic information and provides targeted treatment options tailored to the cancer of the individual. Little is currently known about whether PSCC tumours possess features that would favour intervention with this exciting therapeutic strategy. Vulvar squamous cell carcinoma is another type of HPV-driven malignant cancer. Our previous research suggests that we may have uncovered a novel therapeutic target that could be used in precision medicine. In this study, we will perform a detailed analysis of the genetic and molecular signatures in both HPV-mediated and non-HPV-mediated PSCC tumours. This will enable us to identify potential genes that could be targeted in precision medicine treatments. We will also work to generate original primary models in a wet laboratory to gain further understanding of the molecular landscape of PSCC and ultimately pave the way for the development of superior therapeutic strategies.

Research Team

Principal investigator: Dr. Michael Rauh

Co-investigator: Dr. Sheela Abraham

Host institution: Queen’s University

Plain – Language Summary: A few thousand blood stem cells, found mostly in the bone marrow, contribute to the remarkable production of billions of mature blood cells each day. These blood cells are essential for oxygen delivery to tissues, healing of wounds and prevention of infections. However, as humans age, these stem cells can acquire genetic damage (mutations). On occasion, these mutant stem cells obtain a poorly understood selective advantage, allowing them to produce a disproportionate number of mature blood cells carrying the marker mutation. This condition is surprisingly common, detectable in at least 15% of adults 65 years of age or older, and is called “clonal hematopoiesis” (CH). This is almost always a silent condition, with no symptoms or effects on blood cell counts. However, CH is the first step on the road to a blood cancer and individuals with CH have a 12- to 50-fold increased risk of progressing to a blood cancer like acute myeloid leukemia (AML). At present, it is very difficult to predict who with CH will progress to AML and there are no treatments yet for CH. Unlocking these secrets has tremendous potential. Based on our research, we believe CH cells create an environment of inflammation that favours their expansion over normal blood stem cells. With the complementary expertise of a blood pathologist (Dr. Rauh) and stem cell scientist (Dr. Abraham) we will analyze how mutant blood stem cells condition their environment at the earliest stages of cancer, by secreting tiny “packages” called extracellular vesicles (EVs).

Research Team

Principal investigator: Dr. Brendan Dickson

Co-investigator: Dr. Irene Andrulis, Dr. Jay Wunder, Dr. Kim Tsoi

Host institution: Mount Sinai Hospital

Plain – Language Summary: Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are rare cancers that occur in the limbs. They are unique as they often have large areas of abnormal signal (edema) surrounding the main tumour on MRI. In some patients these abnormal areas contain tumour cells but in others reflect only benign tissue swelling. To treat these cancers effectively, both the tumour mass and surrounding tumour cells must be removed. If any tumour cells are left behind, there is an increased risk of cancer recurrence which can compromise patient survival. There is no way of predicting which abnormal areas contain tumour cells so surgeons remove as much of this tissue as possible. This is not ideal as many patients undergo more invasive surgery than necessary, leading to complications, while others may be undertreated, resulting in cancer recurrence. Currently, cancer cells can only be identified in the tissue surrounding the main tumour by looking at individual sections under a microscope, which is timeconsuming and inaccurate. Our group previously identified the genetic mutations present in a group of MFS and UPS tumours. In this study, we will test whether we can detect these same mutations in isolated tumour cells in the edematous areas surrounding the main tumour mass. We will compare this new technique with microscopic evaluation. We believe that detecting mutations will be more accurate than the current approach and therefore can be used in the future as a personalized surgical planning tool to guide the extent of each patient’s cancer operation.

Research Team

Principal investigator: Dr. Clinton Campbell

Co-investigator: Dr. Hamid Tizhoosh

Host institution: McMaster University

Plain – Language Summary: When a patient is suspected of having a blood or a bone marrow disorder, a bone marrow biopsy study is performed. This study consists of many different parts that are analyzed by pathologist to make a final diagnosis. This is a lengthy and complicated process that may take days to weeks, depending on the type of bone marrow disorder. However, one part of the bone marrow study, known as the aspirate, provides important information within hours of collection that guides further testing, may support a diagnosis and even lead to early treatment in some cases. As part of the aspirate review, a pathologist classifies and counts many different types of bone marrow cells into categories. Based upon the number of cells in each category, further decisions on testing or treatment are made. However, counting bone marrow cells is time consuming, and different pathologists may disagree on which cells fit into each category. These factors may affect the ability of pathologists to correctly diagnose bone marrow disorders. As a result, there is need for new tools that will help pathologists to better analyze bone marrow aspirate cells. Recently, artificial intelligence has been used to perform a number of diagnostic tasks in pathology by analyzing images of cells. Our team will explore the ability of artificial intelligence to help pathologists analyze and count bone marrow cells. This may eventually lead to artificial intelligence technology that will support the ability of pathologists to diagnose blood and bone marrow disorders, toward better outcomes for patients.

Research Team

Principal investigator: Dr. Ami Wang

Co-investigator: Dr. Scott Davey, Dr. Harriet Feilotter, Dr. Michael Rauh, Dr. Tao Wang

Host institution: Queens University

Plain – Language Summary: In 2014, scientists discovered a group of stem cells with genetic mutations in the bone marrow and blood, which is associated with increased risk of heart attack and stroke, blood cancer, and the development of immature dysfunctional blood cells. This condition was termed Clonal hematopoiesis of indeterminant potential (CHIP). CHIP appears to be an age-related phenomenon, which is rarely identified in younger people but can be seen in 30% of the population by age 85.

It is not known why and how CHIP develops, but failure of the immune system in the “search and destroy” mission of abnormal stem cells may play an important role. Age-related changes may potentially lead to a weakened immune system, which allows CHIP to escape and survive in the body’s environment.

Similarly, disruption of the normal function of the immune system is one of the ways that allow cancer cells to grow. A major advancement in cancer treatment is immunotherapy, which is essentially a boost for the body’s own immune system to fight off cancer cells. Immunotherapy has resulted in significantly improved patient survival in various cancers, especially melanoma. The downside of immunotherapy includes treatment toxicities, high cost, and the lack of a predictor for tumour response.

For this study, we aim to determine if immunotherapy in melanoma patients had any impact on CHIP levels. Given that CHIP could be a potential indicator for an individual’s immune status, we hypothesize CHIP may be a biomarker in predicting melanoma patients’ response to immunotherapy.

Research Team

Principal investigator: Dr. Phedias Diamandis

Co-investigator: Dr. Cheryl Arrowsmith, Dr. Ming Tsao

Host institution: University Health Network

Plain – Language Summary: Glioblastoma is the most aggressive form of brain cancer, killing the majority of patients within 12-15 months. Unfortunately, despite numerous clinical trials, life expectancy has only marginally increased over the past 50 years. Glioblastoma infiltrates surrounding brain tissue at early stages of disease making surgical management difficult. Traditional laboratory approaches designed to model cancer (i.e. growing isolated cancer cells in dishes or mouse brains) are not favorable tools for evaluating response to new therapeutic agents due to their limitations and over simplification of this complex disease. Therefore, there is urgent need to develop more representative model systems to study glioblastoma.

Advances in tissue engineering now allow scientists to transform stem cells into three-dimensional, brain-like structures called “cerebral organoids”. Under the microscope, these organoids show human-specific tissue-like architecture providing mini laboratory “avatars” of human brain tissue. In addition to allowing scientists to study how a brain develops, this technology enables researchers to introduce cancer cells into these mini-brains to form structures termed “brain tumour assembloids”. This complex culture system thus provides a more accurate model to simulate how patient glioblastomas grows within these engineered 3D human brain tissue elements. The small size of these structures also allows scientists to simultaneously expand and maintain hundreds of these cerebral organoids, creating a convenient platform for personalized glioblastoma drug screening. Establishment of a brain tumour assembloids screening platform will thus provide patients with a large array of personalized laboratory avatars that, in the future, can help guide individualized selection of empirically effective non-toxic therapies.

Research Team

Principal investigator: Dr. Rashmi Goswami

Co-investigator: Dr. Rena Buckstein

Host institution: Sunnybrook Health Sciences Centre

Plain – Language Summary: Myelodysplastic syndromes (MDS) are cancers that can cause infection or bleeding because they prevent the formation of blood components, such as red blood cells, white blood cells, and platelets. MDS can also cause leukemia which can lead to a patient’s death. MDS can be caused by changes (or mutations) to a patient’s DNA. There have not been any studies to see if these mutations cause an increased risk of heart disease in MDS patients, although it is known that MDS patients do have an increased risk of heart disease compared to healthy adults. We will look at these mutations and see if they are linked to an increased risk of heart disease. We will also use “CT imaging” to see if MDS patients have artery disease that isn’t causing symptoms but may lead to heart disease in the future and if that is related to the mutations that they have. We also think that the mutations seen in MDS patients lead to inflammation which leads to heart disease, so we will try to link mutations in MDS patients to markers of inflammation to see if there is a pattern between them as well as the amount of artery disease we see on CT imaging. We are looking to find mutations that are associated with inflammation and heart disease. This will allow us to make sure that MDS patients with these mutations are tested and/or are treated early on for heart disease so that they have a better and longer life.

Research Team

Principal investigator: Dr. Michael Cabanero

Co-investigator: Dr. Ming Tsao, Dr. Daniel De Carvalho, Dr. Scott V. Bratman, Dr. Benjamin H. Lok, Dr. Geoffrey Liu

Host institution: University Health Network

Plain – Language Summary: Lung cancer is the most common cancer killer worldwide. Small cell lung cancer (SCLC) is an extremely aggressive type of lung cancer that represents about 1 in 7 of all lung cancer cases. SCLC patients live on average about 8-12 months and only 7 in 100 patients survive to 5 years. Two chemotherapy drugs are given to essentially all patients and are called cisplatin and etoposide. They have been proven to extend life for patients because the cancer is initially very sensitive and shrinks when treated by these two drugs. But for the vast majority of SCLC patients, the cancer eventually grows again and is no longer responsive to additional treatments with cisplatin and etoposide. In addition, some patients with SCLC are resistant to chemotherapy upfront. However, a path way forward has been our increasing understanding of how cancer also corrupts changes on top of our genetic code (i.e. epigenetics) without directly altering the genetic code. One of the greatest challenges in examining SCLC epigenetics is lack of adequate tumor samples as they are difficult to obtain. We will address this limitation by maximizing use of patient blood samples to address our research goals. This project is designed to understand the epigenetics of SCLC and to develop a molecular biomarker to predict treatment response from the plasma (i.e. “cell-free”) portion of patient blood samples. In addition, we will generate renewable cancer models from circulating tumor cells extracted from patient blood samples for correlation with our cell-free epigenetic molecular biomarker.

Research Team

Principal investigator: Dr. Neil Renwick

Co-investigator: Dr. Simron Singh

Host institution: Queens University

Plain – Language Summary: Neuroendocrine tumors (NETs) are clinically diverse neoplasms that affect males and females of all ages and race. Because NETs are hard to diagnose and resource intensive to monitor, better blood tests are needed to guide clinical care. MicroRNAs (miRNAs) are small RNA regulatory molecules that can be excellent biomarkers due to their tissue specificity. While generating an updated atlas of human miRNA expression atlas, my team and I found that miR-375 is abundantly expressed in all NET tissues. The goal of this proposal is to lay the groundwork for a simple miRNA-based blood test to diagnose and monitor all NETs. Our hypothesis is that neuroendocrine cell-specific miR-375 is a circulating marker of NET disease burden. This hypothesis is formulated from extensive, yet incomplete, miRNA expression profiling of NET and control tissues and cell lines in the Renwick lab. We will test our hypothesis through two objectives to: i) consolidate knowledge of miRNA expression in NET and control tissues, and ii) establish and pilot plasma total small RNA profiling for persons with and without NETs. The rationale for our research is to provide doctors with a reliable, accurate, and inexpensive tool for guiding NET clinical care. This proposal represents a new trans-institutional collaboration between Dr. Neil Renwick at Queen’s University and Dr. Simron Singh at Sunnybrook Health Sciences Center and is firmly aligned with the mission of OMPRN to enhance molecular pathology research capacity across Ontario.

Research Team

Principal investigator: Dr. Philip Berardi

Co-investigator: Dr. Isabelle Bence-Bruckler, Dr. Trevor Pugh

Host institution: The Ottawa Hospital/University of Ottawa

Plain – Language Summary: Diffuse large B-cell lymphomas are a commonly diagnosed and diverse group of aggressive malignancies that have distinct clinical and molecular features that do not always correlate with their appearance under the microscope. Advances in the genetic and molecular understanding of these cancers has highlighted the importance of having an accurate and reliable method for classifying them into different subtypes as there are significant differences in their genetic and molecular characteristics, differences in patient outcomes, and there are various therapeutic options depending on the risk profile associated with each subtype. Furthermore, the subtype has been proposed to be included in a screening method used by pathologists to test for genetic alterations that would classify the diffuse large B-cell lymphoma as aggressive or ‘high-grade.’ As the commonly used subtyping algorithm shows suboptimal accuracy and reliability and poor inter-laboratory reproducibility, we aim to study how a new diagnostic testing approach that shows promise as an accurate, reliable, and cost-effective replacement for the standard method currently in practice. This new method may also help with the investigation of new markers that can help predict the outcome in more challenging cases that have been historically categorized as unclassifiable and help screen for mutations that confer a worse patient prognosis.

Research Team

Principal investigator: Dr. Prodipto Pal

Co-investigator: Dr. Randy Van Ommeren, Dr. Natasha Leighl

Host institution: University Health Network

Plain – Language Summary: Artificial intelligence (AI) research has advanced significantly in recent years, and has given rise to algorithms which are adept at analyzing image data. The application of this technology within pathology is an area of major interest, since these algorithms may be able to help pathologists diagnose cancer with increased accuracy, consistency, and efficiency. Past research has shown that there is considerable variability between the diagnoses of individual pathologists, and the use of diagnostic software promises to bring an added element of objectivity to the diagnostic process. Furthermore, it may become possible to use this software to predict the types of mutations found in a tumour, information which is usually obtained using time-consuming advanced testing techniques. Since many treatments in lung cancer are based on the individual mutations in a patient’s cancer, obtaining this information very rapidly may be allow a patient’s physician to initiate therapies immediately while waiting for definitive test results. Finally, these algorithms may not only be useful for diagnosing known types of cancers, but may help to identify new types of lung cancer which share subtle microscopic features that are not easily visible to the human eye. Since tumours which share microscopic features frequently have similar biological characteristics, identifying new subtypes may help pathologists to classify patients’ tumours, and refine predictions about patients’ expected treatment response and prognosis.

Research Team

Principal investigator: Dr. Bibianna Purgina

Co-investigator: Dr. Jean-Simon Diallo

Host institution: Ottawa Hospital Research Institute

Plain – Language Summary: Liposarcoma, a malignant cancer arising from fat cells, only responds to chemotherapy 24% of the time and treatment options have not changed in many years. Our long-term goal is to create an immunotherapy treatment that leverages the patient’s own immune system to recognize and destroy the malignant cells. The first vital step in this process is to identify proteins (antigens) for the immune system to target that are unique to the sarcoma cells and not present in the normal cells of the body. A group of proteins that hold great potential for this purpose are called cancer-testis (CT) antigens. For this project, we intend to survey low and high grade liposarcoma for CT antigens by immunohistochemistry (IHC), a process that tags the antigens, if present, with a coloured pigment visible by microscopy. In addition, using IHC as well as cutting edge technology called nanostring that can probe over 700 genes simultaneously from very little material, we will study the immunological status of these liposarcomas to inform the development of the right type of immunotherapy for the right patients. In addition, we will use nanostring results regarding CT antigens to direct further research in cases with low expression of the CT antigens previously tested. Overall, we hope these studies will serve as a springboard for developing new immunotherapies targeted towards liposarcoma.

Research Team

Principal investigator: Dr. José-Mario Capo-Chichi

Co-investigator: Dr. Anne Tierens, Dr. Melanie Care

Host institution: University Health Network

Plain – Language Summary: Blood cancers can be acquired (in the tumoral blood tissue only) or inherited (present in any cells). DNA mutations can be identified in the blood of any individuals with blood cancer. 11-37% of patients with acquired blood cancers also bear the same mutations in any cells of their body including their gonads; these mutations can therefore be transmitted to their offspring and predispose them to familial blood cancers. In addition, patients with blood cancers may receive transplants from related family members (e.g. siblings, parents). As familial blood cancers are very frequent in patients with acquired blood cancers, their family related cell donors may be affected with a yet undiagnosed cancer; putting the patient at significant risk of morbidity . The Genome Diagnostics Laboratory at the University Hospital Network (GD-UHN) is funded to test patients with acquired Acute Myeloid Leukemia (AML) in Ontario, but genetic testing for mutations predisposing to inherited blood cancers is not offered in Canada. Currently, there is no way at GD-UHN to tell if a patient has acquired or familial AML. It was shown that patients with familial susceptibility to blood cancers have high levels of disease-causing mutant DNA in their blood tissue; it is then possible to screen for individuals at risk of familial blood cancers by looking at the amount of mutant DNA in specific genes from blood analysis. In this study, we aim to use the levels of mutant DNA4 results from tumor of AML patients to predict their risk of familial blood cancer.

Research Team

Principal investigator: Dr. Bojana Djordjevic

Co-investigator: Dr. Arun Seth

Host institution: Sunnybrook Health Sciences Centre

Plain – Language Summary: Treatment of endometrial (womb) cancers includes surgery (removal of the womb) or hormonal treatment, depending on the degree of severity and spread of disease. There is a growing interest in hormonal treatment for patients wishing to have children or patients that have other medical conditions which prevent them from having surgery.3 Hormonal treatment includes progesterone based therapy, which is currently reserved for precursor lesions and early low grade endometrial cancer (grade 1). However, not all cases respond to hormonal treatment or some tumors recur after treatment. Moreover, some women with cancers of intermediate grade (grade 2) are also interested in hormonal treatment in order to delay surgery and allow time for a successful pregnancy. A current challenge in management of these cases is to identify patients who would respond to hormonal treatment and for whom surgery can be safely delayed. Our aim is to study the molecular profile of intermediate grade cancers and compare them to that of endometrial precancer and low grade cancer that have a known response to progesterone therapy. We believe that a proportion of intermediate grade cancers resemble the low grade responsive cases, which would suggest that select intermediate grade cases can also be safely treated with progesterone. Knowing which patients would benefit from hormonal treatment before starting therapy would allow a better management of cases in clinical practice.

Research Team

Principal investigator: Dr. David Berman

Co-investigator: Dr. Robert Siemens

Host institution: Queen’s University

Plain – Language Summary: Currently, testing men to diagnose prostate cancer requires biopsies that often lead to serious complications such as bleeding or infection. We have developed a test that identifies cancer specific chemical modifications to DNA in specific genes. The test is more than 90% accurate when applied to prostate tissue samples.

In the proposed work, we will develop procedures for testing urine instead of biopsy tissue. The urine test should more accurately identify men with and without prostate cancer, thereby preventing unnecessary biopsies and saving men from related complications.

Research Team

Principal investigator: Dr. Hubert Tsui

Co-investigator: Dr. Vikas Gupta

Host institution: Sunnybrook Health Sciences Centre

Plain – Language Summary: Myeloproliferative neoplasms such as primary myelofibrosis (PMF) are a type of blood cancer where the normal production of red cells, white cells or platelets becomes uncontrolled. In PMF, this abnormal function eventually leads to scarring of the bone marrow and potentially changes the disease from making too many blood cells to making too few. Sometimes, this may even result in a medical emergency called acute leukemia where the bone marrow is scarred but the blood cells that are still being made are all primitive. Aside from bone marrow transplant, there are some drugs that can help slow down the scarring process. Unfortunately, the beneficial effect of these drugs wears out over time in some patients but not others. We do not understand why that is the case but a clue may lie in the kind of scarring that is occurring in the bone marrow. Using special stains, it appears that there are different patterns of scarring in PMF patients, which may explain why some patients do better on therapy. In order to potentially match the right PMF patient to the right therapy, it will be useful to investigate what causes the different kinds of scarring patterns. We plan to use protein, DNA and RNA based technology to explain how the blood cancer and the non-cancer scar-forming bystander cells interact directly in the marrow itself. Hopefully, by focusing on where the scar formation is actually occurring, we will be able to discover new information for personalized treatment.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Elizabeth Demicco

Co-investigator: Dr. Jay Wunder

Host institution: University of Toronto & Mount Sinai Hospital

Plain – Language Summary: Solitary fibrous tumors (SFT) are slow-growing tumors which may arise anywhere in the body. SFT spread throughout the body (“metastasize”) in 10-30% of patients. SFTs are caused by a DNA alteration which joins (“fuses”) the first part of the NAB2 gene with a portion of the STAT6 gene. The amount of DNA from each gene present in the resulting NAB2-STAT6 fusion gene may affect the behavior of tumors. We have devised a model to predict which SFT will spread after surgical removal, but do not understand what causes these different behaviors. Metastatic SFT are treated with drugs to prevent further growth, but often do not respond.

Our study seeks to 1) explain the observed differences between SFT with different NAB2-STAT6 fusions, 2) identify factors which can be used to predict the behavior of SFT after removal or which affect the ability of SFT to respond to drugs.

To answer these questions, we will compare gene expression (mRNA) between SFT with low risk of metastasis and malignant SFT (those with history of metastasis). We will also compare SFT containing different NAB2-STAT6 DNA fusions. We will use these data to learn about which cellular processes are over-active in the malignant tumors, or are different between SFT with different NAB2-STAT6 fusions. We will confirm the expression of the most promising factors in tumor tissues using immunohistochemical stains. We expect these studies will provide us with new prognostic markers, as well as markers to better guide drug therapy in individual patients with SFT.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Carlos Parra-Herran

Co-investigator: Dr. John Bartlett

Host institution: Sunnybrook Health Sciences Centre

Plain – Language Summary: Accurate diagnosis of ovarian mucinous carcinoma (OMC), a rare type of ovarian cancer, is currently challenging. Pathologists, as doctors specialized in laboratory medicine, have traditionally diagnosed OMC based on specific features seen under the microscope.

Nevertheless, this approach is insufficient for accurate distinction between cancers that originate in the ovary (which have an overall good prognosis) from cancers that originate somewhere else and metastasize to the ovary (which have a poor prognosis, they usually arise in the gastrointestinal tract). This distinction is important, not only because the differences in prognosis but also because the ovarian metastasis may be the first sign of disease in a patient with an otherwise occult cancer elsewhere; determining where the metastasis is coming from is vital to direct chemotherapy, radiation and any other treatment. Given the limitations in the tools that the pathologist has for this exercise, diagnosis of a OMC is often inconclusive and further clinical and radiologic investigation is required to find a possible primary tumor, leading to expenditure of time and resources and patient anxiety.

Recently, it has been shown that genetic analysis of mutations in ovarian cancer may help better diagnose disease subtypes and predict their biological behavior. However, due to the rarity of the disease, OMC is underrepresented in such studies, thus its status within the classification system of the disease has not been elucidated. This study aims to characterize the global genetic makeup of OMC using a technology known as “next-generation” sequencing. In this manner, researchers hope to identify a set of genetic alterations unique to OMC to build individual molecular profiles that will help doctors make better decisions to care for their patients. Additionally, analyzing the genetic differences between primary and metastatic cancer may demonstrate the value of a customized molecular panel in diagnosis, determination of prognosis and treatment decision-making for patients with this disease. Lastly, this study may also help identify new targeted therapeutic treatment options for women with OMC.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. David Hurlbut

Co-investigator: Dr. Christine Orr, Dr. Nazik Hammad

Host institution: Queens University

Plain – Language Summary: Fundamental to how a cancer cell develops and grows is an understanding of the subcellular machinery (gene signaling pathways) that are abnormal (dysregulated). This understanding forms the basis for testing potential anti-cancer treatments to improve patient survival. The overall aim of this project is to improve our understanding of key signaling pathways in colorectal cancer (CRC) cells that are important in tumour growth. We are interested in studying diabetic patients with CRC because these patients, when treated with oral hypoglycemic drug Metformin, have improved survival compared with other CRC groups. Metformin is believed to deplete the energy level of cancer cells and dysregulate the subcellular machinery that impairs cell growth and cancer spread. In this study we will look at the activity (expression) of genes that are associated with these cancer subcellular pathways in tumour samples from 100 diabetic CRC patients (50 Metformin treated versus 50 diet treated) for which we have detailed clinical (including survival) data. We expect that those genes that have abnormal expression in CRC cancer cells in the Metformin treated group when compared to the diet only group will be linked to better clinical outcome and will help identify subcellular pathway(s) associated with the anti-tumour effect of Metformin. This will improve our understanding of potential important components of the tumour subcellular machinery (gene/protein signaling pathways) that should be targeted to help reduce cancer risk and poor outcome.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Yening (Daniel) Xia

Co-investigator: Dr. Kenneth Aldape

Host institution: University Health Network

Plain – Language Summary: Pathologists are responsible for the accurate classification (or categorization) of human diseases, including cancers (e.g. distinguishing breast cancer metastatic to the lung from primary lung cancer).

Only when appropriately classified can patients with cancers receive the optimal site-specific treatments. While the examination of tissue samples under the microscope by pathologists is usually sufficient for achieving this end, there often remains a small percentage of cases that are subject to diagnostic discrepancies and/or may be otherwise difficult to classify.

For this, DNA-methylation profiling, by providing tumor tissue-of-origin signatures (e.g. breast versus lung), is a potentially useful adjunct. While recent research studies produced very promising results, the profiling technology itself is technically demanding and may be difficult for clinical laboratories to adopt. Accordingly, the goal of this project to simplify methylation-based cancer classification, in part by reducing the number of markers needed. In a preliminary study, using just 28 selected markers (rather than all 27 thousand available markers), we were able to correctly assign ~90% of >1000 cancer cases to their tissues-of-origins.

With funding, we will perform additional analyses and test additional samples with the goal of designing a practical and effective methylation-based test that could be validated for routine clinical use in a follow-up study. All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. George Yousef

Co-investigator: Dr. Rola Saleeb, Dr. Georg Bjarnason

Host institution: University of Toronto

Plain – Language Summary: We are studying a type of kidney cancer called the papillary type. This type of cancer is particularly common in diseased kidney. Findings from our previous work as well as the work of others led us to believe that these cancers arise from kidney regenerative cells.

These cells are normally hidden in the kidney, but when the kidneys start to shows signs of damage, these regenerative cells are increased in number so as to renew/regenerate the lost cells. Though they should be helpful to the kidney, some disruption in their biology happens at that stage which makes them give rise to cancer. It is important to note that there are small lesions termed papillary adenomas that are also very common to find in the damaged kidneys that look identical to the cancer we study (but smaller) and are though to give rise if left to the full blown cancer. So in essence these lesions are the link between the regenerative cells and the cancer. In this project we will study that proposed connection between these regenerative cells and the cancer by tracking the cells all through from the normal kidney, to the damaged kidney to the small adenoma lesions to the cancer. Through that process we will understand a lot more about the biology of how these cancers form.

That knowledge will help us in the future to prevent these kidney cancers. All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Susan Done

Co-investigator: Dr. Philippe Bedard, Dr. Willard Wong

Host institution: University Health Network

Plain – Language Summary: Characteristics of breast cancer tissues can be used to predict outcomes for patients with cancer, and help to choose their appropriate treatment. Some cancer cells can enter the blood stream from the breast and travel to distant sites throughout the body. Breast cancer is the most commonly diagnosed non-skin cancer among women. Blood drawn from many patients contain circulating tumour cells (CTCs). We aim to study features of circulating tumour cells in patients with breast cancer, which we hope will provide a means of guiding treatment.

Previously we studied a group of 17 breast cancer patients and identified several genes that were often changed in these cells. We now need to study CTCs from a bigger group of breast cancer patients to confirm the importance of the changes we have found. We will extract breast cancer cells from the blood of 50 women being treated at Princess Margaret Cancer Centre. We will see if the genetic changes we have found can provide more information to treat breast cancer or predict how the cancer may behave. In terms of impact, studying circulating tumour cells could become a cheaper and minimally-invasive tool to affect treatment of disease, and would lead to more tolerable detection of cancer and financial savings for Canadian healthcare. Not only can this study of circulating tumour cells be used in breast cancer, it can also be extended to other cancer in the future.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Terence Moyana

Co-investigator: Dr. Julian Little, Dr. Anthea Paul

Host institution: The Ottawa Hospital & The University of Ottawa

Plain – Language Summary: Colorectal cancer (CRC) is a world-wide health problem especially in wealthier countries and the numbers for CRC are going up. An 80% increase in CRC deaths is projected by 2030 unless there are significant improvements in prevention, early disease detection and treatment. CRC usually develops from polyps that over time change to cancer. Therefore early disease detection improves outcomes. Colonoscopy is the gold standard for detection of CRC, but it is costly and invasive for screening purposes. Fecal-based tests are for useful for screening but they are not very sensitive or specific. Therefore, more accurate, non-invasive tumor biomarkers for the detection of early CRC lesions (ECRCL) are required. There is growing evidence about the role played by microRNAs (miRNAs) human cancer. Tumor-specific circulating miRNAs can be detected in the blood of various cancer patients including CRC. The circulating miRNAs are highly stable and can therefore be useful diagnosing and predicting cancer. The main objectives of this project are to: i) investigate circulating miRNA expression profile in blood from patients with ECRCL and compare them with healthy controls  ii) evaluate miRNA expression profile in ECRCL as well as adjacent mucosa and iii) identify disease specific miRNA signatures that are typical of ECRCL.  This research project will advance knowledge on the role of circulating miRNAs biomarkers in CRC diagnosis and their potential predictive role for disease risk assessment. The findings will help in developing a panel of circulating miRNAs markers usable for accurate early detection of CRC, and improve CRC screening strategy.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Blaise Clarke

Co-investigator: Dr. Ju-Yoon Yoon, Dr. Philip Awadalla

Host institution: University Health Network

Plain – Language Summary: In the Canadian health care system, we are often bound by the fiduciary restrictions, and diagnosing rare tumours can be particularly challenging. Research from our group and others have identified that DNA sequencing technology can allow us to accurately diagnose these tumours, allowing the patients to appropriately seek genetic counselling and/or potentially receive new drug that target those mutations. Two barriers prevent such advances: 1) cost of the new tests, and 2) lack of a validating study that confirms the presence of those mutations in a larger group of patients. At the Toronto General Hospital (TGH), we have accrued a large group of cases that would allow us to tackle those two challenges. With a large number of surgeries at TGH, we have enough number of these relatively rare ovarian cancers that would allow us to confirm the presence of those mutations and examine their frequency. Using state-of-the-art DNA sequencing technology available at TGH, we aim to construct a novel sequencing panel that would serve as a one-stop test for a number of these tumours, allowing us to identify these mutations with a single run. We potentially have a solution to the aforementioned barriers that would allow for truly personalized care of these patients. With the TGH.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Michael Rauh

Co-investigator: Dr. Harriet Feilotter

Host institution: Queens University

Plain – Language Summary: Myeloid cancers arise in the blood cell factory known as the bone marrow.  They occur when blood stem cells acquire genetic changes that impart a growth advantage.  This also disturbs the natural balance of blood cell production, causing patients to present with fatigue (decreased oxygen-carrying red cells), bruising or bleeding (decreased blot-clotting platelets), or increased infections (decreased microbe-fighting, mature white cells).  Myeloid cancers range in severity from myeloproliferative neoplasms (MPN), to myelodysplastic syndromes (MDS), to acute myeloid leukemia (AML).

Myeloid cancer diagnosis has historically relied on changes detected under the microscope, and limited, low-resolution genetic tests that take time to obtain.  This has led to challenges with diagnosis, particularly for MDS, and mostly one-size-fits-all treatment.  As myeloid cancers increase with age, we must do better to prepare for and serve our aging population.

Our strategy for Path2MyDx is to improve diagnosis and treatment options for myeloid cancer patients by advancing testing.  We will utilize a “next-generation” sequencing (NGS) test that incorporates objective, personalized genetic information from DNA and RNA, with high throughput and a rapid turnaround time.  In this way, we will build individual molecular pathology profiles that help clinicians to diagnose myeloid cancer earlier and more precisely, while better informing patient risk and guiding treatment decisions.  Beyond diagnosis, we also believe NGS will help clinicians monitor and fine-tune treatment in real time, to better manage patients with myeloid cancers.  Finally, we will learn from this pilot, share our knowledge with other centers, and advocate for this NGS test to be funded by government.

Research Team

Principal investigator: Dr. Sonal Varma

Co-investigator: Dr. Peter Greer

Host institution: Queens University

Plain – Language Summary: This study is looking at biomarkers in tissue samples of people with breast cancer to help tell which patients will respond to chemotherapy.

Researchers believe that activity of a protein called ezrin can increase a patient’s risk of developing advanced breast cancer, which does not respond to chemotherapy. In this study researchers will develop a test, using tissue samples from current breast cancer patients, which can be used to figure out the level of activity of this protein in an individual’s tissue sample and what impact this has on whether their cancer will respond to chemotherapy.

Researchers also believe that patients with a decreased level of ezrin protein activity may be more sensitive to two drugs called doxorubicin and paclitaxel. Researchers hope that this test will help doctors predict which patients will benefit from these treatments or a combination of these treatments.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Phedias Diamandis

Co-investigator: Dr. Paul Boutros

Host institution: University Health Network

Plain – Language Summary: This study aims to identify new markers of aggressiveness in tissue samples of patients with meningiomas (a type of brain tumour). Although many patients with meningiomas do well following surgery, some tumours recur and can behave very aggressively. These types of meningiomas are referred to as clinically malignant meningiomas. It is important identify clinically malignant meningiomas as they have significant implications to a patient’s expected outcome and treatment plan.

Doctors have traditionally made predictions regarding the biological behavior of meningiomas based on specific features seen under the microscope. It has however proven difficult to accurately predict when meningiomas will behave aggressively and return after surgery using this tool. Identification of better predictors of clinically aggressive meningiomas are thus needed.

As has now been shown in many cancer types, “molecular” analysis of meningiomas may help better predict their biological behavior. Specifically, for this project, using a technology known as mass spectrometry (MS), the global protein makeup (proteome) of tumors will be analyzed. Because proteins, the products of genes, are directly responsible for carrying out most of a cell’s function, their levels are thought to be a strong measure of biological activity. Analyzing the protein differences between benign and cancerous meningiomas may thus allow the discovery of new markers that can better predict the likelihood that a meningioma is malignant. In this study, researchers will analyze meningioma tissue samples from patients with either benign and malignant behavior in attempts to find protein patterns specific to each type.

Researchers believe that patients with a protein pattern indicative of an aggressive meningiomas can benefit from radiotherapy after surgery to help prevent tumor recurrence. Researchers hope that this test will help doctors predict which patients will benefit from this additional treatment and which patients will not. This will also help provide reassurance and prevent over-treatment of patients will less aggressive meningiomas.  Lastly, analysis of the protein make-up of meningiomas may also help identify new less-invasive and less-toxic therapeutic targets for all patients suffering from meningiomas.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Bojana Djordjevic

Co-investigator: Dr. Arun Seth

Host institution: Sunnybrook Health Sciences Center & University of Toronto

Plain – Language Summary: This study is looking at biomarkers in tissue samples of people with early endometrial (womb) cancer to help tell which patients can avoid having surgery.

Endometrial cancers, which have not grown beyond the womb lining are considered localized, these can often be treated with surgery with or without radiotherapy. However surgery for these patients means partial (removal of the womb) or complete hysterectomy (removal of the womb and ovaries) and can be life-changing for patients wishing to have children or not possible for patients who cannot undergo surgery because of other health conditions.

Researchers believe that womb cancer patients with a change in a type of protein which regulates the hormone progesterone, could put these patients at higher risk of their tumour spreading. Patients with changes to this protein, called progesterone receptor isoforms, PR-A and PR-B, may respond better to a type of hormone therapy called progestin. In this study researchers will develop a test, using tissue samples from current womb cancer patients, which can be used to figure out if this type of protein change is present in an individual’s cancer and what impact this has on their tumour spreading.

Researchers will also test whether patients with these protein changes respond better to progestin. Researchers hope that this test will help doctors predict which patients will need surgery and which patients can be given hormone therapy.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Elizabeth McCready

Co-investigator: Dr. Guillame Paré, Dr. Laila Schenkel

Host institution: McMaster University

Plain – Language Summary: This study is looking at biomarkers in tissue samples of people with gliomas (a type of brain tumour) to help tell which patients are more likely to respond to different treatments available.

Some gliomas develop as a result of changes in a patient’s genes or a number of different changes in different genes. Understanding which changes have occurred in a patient’s cancer can help to identify treatments which the patient is more likely to respond to.

Methylation is a process in which certain chemicals called ‘methyl groups’ are added to proteins, DNA and other molecules to make them active or inactive. Researchers believe that looking at where methyl groups have been attached can show which genes have been changed. Researchers will use tissue samples from current glioma patients to develop this pattern of methyl groups into a test so that doctors can figure out which gene changes are present in an individual’s cancer. Researchers hope that this test will help doctors match patient with gliomas to treatments which target these changes.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Alan Tuck

Co-investigator: Dr. Ann Chambers, Dr. Matthew Cecchini

Host institution: London Health Sciences Center

Plain – Language Summary: This study is looking at biomarkers in tissue samples of people with Ductal Carcinoma In Situ (DCIS) to help tell which patients will develop invasive mammary carcinoma (an advanced form of breast cancer).

Ductal Carcinoma In Situ (DCIS) means cells inside some of the ducts of the breast have started to turn into cancer cells. These cells are inside the ducts and have not started to spread into the surrounding breast tissue. Doctors diagnose DCIS by looking at whether or not cells within the ducts of a patient’s tissue sample appear benign (non-cancerous) or malignant (cancerous).  However, only some of these patients will go on to develop invasive breast cancer and it is currently difficult for doctors to tell which of these patients are at risk.

Researchers believe that increased activity of the T-box transcription factor (TBX3) gene is linked to more aggressive breast cancer. In this study researchers will assess which other genes are potentially regulated by TBX3, and will use tissue samples from current breast cancer patients to determine whether increased activity of this gene, and/or specific genes that this gene itself activates (such as Slug and Twist1) might be used as an indicator of the potential to break out of the ducts and invade adjacent breast tissue (i.e to become more aggressive).Researchers hope that one or more of these tests will help doctors predict which patients are at risk of progressing to advanced breast cancer.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. George Yousef

Co-investigator: Dr. Antonio Finelli, Dr. Rola Saleeb

Host institution: St. Michael’s Hospital

Plain – Language Summary: Kidney cancer includes multiple subtypes. Papillary renal cell carcinoma (PRCC), the cancer we are proposing this research for, is the second most common form of kidney cancer. However PRCC itself is divided into two subtypes, the PRCC type 1 and PRCC type 2. That is based upon the way they look under the microscope. Previous researches have noted that type 2 is usually a more aggressive form of cancer than type 1. As such patients with these cancers should be followed differently. Other studies as well as ours have found that the types have a different biology.  Therefore their response to cancer drugs is expected to be different. However to date, they are treated by doctors as one entity.

Part of the dilemma is that nearly half the cases are hard to subtype using the microscope alone. There is a need for a test (biomarker) that can help Pathologist’s (cancer microscope doctors) distinguish between them. Our previous work identified some possible promising markers. We need to confirm these results in another set of cancer patients, which is part of our research proposal. The findings will help doctors divide patients properly in the right group for follow up and treatment.

Yet another confounding factor is that, even though the types are known to have different biology, the exact nature of these changes and how they affect the cancer response to drugs is not properly understood. Our previous research shows that the cancer types should respond differently to certain cancer drugs. We propose studying these differences further and assessing the response of the cancer cells (cancer cells made and grown for research, corresponding to our particular tumor types) to a number of current cancer medications. The results are expected to guide doctors into giving the patients, the right kind of medicine for the right kind of cancer.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Cynthia Hawkins

Co-investigator: Dr. Mary Shago, Dr. Michelle Axford

Host institution: The Hospital for Sick Children

Plain – Language Summary: This study is looking at biomarkers in tissue samples of children with cancer to help diagnose their cancer and to tell which patients are more likely to respond to different available treatments.

Some pediatric (childhood) cancers develop as a result of changes in the genes’ code and/or the number of copies of the genes (gains or losses of the gene). Researchers believe understanding which changes have occurred in a child’s cancer can help to diagnose the cancer and to identify treatments to which the child is more likely to respond. In this study researchers will use a test normally used to for adult cancers and adapt this for children with cancer. Researchers will use tissue samples from current patients with childhood cancer to develop this test so that doctors can figure out which gene changes are present in an individual’s cancer. Researchers hope that this test will help doctors to better match children with cancer to treatments.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. David Berman

Co-investigator: Dr. Kevin Yi Mi Ren, Dr. Igor Jurisica

Host institution: Queen’s Cancer Research Institute

Plain – Language Summary: This study is looking at biomarkers in tissue samples of people with bladder cancer to help tell which patients are at risk of their cancer progressing.

Doctors diagnose bladder cancers by looking at how far cancer tumors have grown into the bladder. Most of these patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). This means the cancer is only in the innermost layer of the bladder lining or has started to grow into the connective tissue beneath the bladder lining. NMIBC can often be treated with surgery.

A small number these patients will progress to advanced bladder cancer. This means the cancer has started to grow beyond the bladder lining and into the surrounding muscle or other parts of the body. Half of these patients with advanced bladder cancer will have incurable disease.

Researchers believe that two gene networks, Sonic HedgeHog (SHH) and Bone Morphogenetic Protein (BMP), are linked to more aggressive bladder cancer when they are turned off. In this study researchers will develop a test, using tissue samples from current bladder cancer patients, which can be used to figure out if these networks are turned off in an individual’s cancer. Researchers hope that this test will help doctors predict which patients are at risk of progressing to advanced bladder cancer.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.

Research Team

Principal investigator: Dr. Blaise Clarke

Co-investigator: Dr. Michael Herman Chui, Dr. Trevor Pugh

Host institution: University Health Network

Plain – Language Summary: This study is looking at biomarkers in tissue samples of people with endometrial (womb lining) cancer to determine which patients might respond to targeted therapies.

Endometrial cancers, which have not grown beyond the womb are considered localized. These can often be treated with surgery with or without radiotherapy. Cancers which have advanced beyond the womb are considered advanced and are less likely to respond to treatment.

Researchers believe that some patients with endometrial cancer have a specific genetic defect, in a gene called MLH1, and belong to a special category, called “Mismatch Repair-deficient”.  In this study, researchers will develop a test, using tissue samples from current endometrial cancer patients, which can be used to figure out if this type of gene mutation is present in an individual’s cancer and will allow doctors to determine if other family members are at also at increased risk for cancer.

Researchers also believe that patients with this type of gene mutation may respond better to a new and highly promising treatment called immunotherapy; so this test will also help doctors predict which patients might benefit from this treatment.

All studies funded by the OMPRN also have an educational objective for trainee pathologists or early career pathologists. Ensuring new researchers have experience in conducting or leading studies helps the OMPRN to develop the next generation of molecular pathology leaders in cancer research.