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Gynecological Cancer Projects 

Early Diagnosis of endometriosis-associated ovarian cancer by leveraging exosomes in endometriotic peritoneal fluid

The early detection of ovarian cancer is crucial to improve the low survival rate currently seen in patients. By examining new approaches to identify women with higher risk of developing this type of cancer, we can work towards improving the survival rate. In recent years we have learned that two ovarian cancer subtypes are more prevalent in patients with a known history of endometriosis. It was shown that both ovarian cancer and endometriosis have some cancer-related mutations in common. Although, these mutations can be found in the diseased tissue, no-one has attempted to detect them through body fluids, which can be accessed through a less invasive procedure. In a proof-of-principle study we will examine the feasibility to detect cancer-related mutations in fluid found within the body cavity of women suffering from endometriosis. We postulate that the detection of these mutations in fluid from the body cavity can serve as a new marker to identify women with higher ovarian cancer risk. A positive study outcome will highlight new possibilities and illustrate feasible new approaches to finding reliable early detection measures for ovarian cancers. 

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Lead: Dr. Karolin Heinze

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Project: Early Dx of EAOC using PF

Precision Medicine for Endometrioid Ovarian Cancer

Ovarian cancers are 5 distinct diseases. One of these, endometrioid ovarian cancer, is hugely different from other ovarian cancers and instead is like uterine cancers. Treating this type like other ovarian cancers is inefficient and for many women results in unnecessary toxic chemotherapy.  

Within endometrioid ovarian cancers, there are four subtypes. The subtyping scheme uses specific protein and gene markers to define 3 of 4 classes, representing 25-30% of cases and this does well to define endometrioid ovarian cancer that needs little vs aggressive treatment. The 4th class, representing ~70% of cases, is a subtype by omission and lacks the markers that define the other 3 groups. It is often referred to as “No Specific Molecular Profile” – a misleading moniker given this subtype can itself be divided up using additional markers of disease.  

 

To bring clarity to this largest subtype of endometrioid ovarian carcinomas we will re-evaluate biological characteristics in a large series of cases. We will also use cells derived from these unique ovarian cancers, grown outside the body (in vitro) or in animal models (in vivo), to contrast different treatments that target biological features common to this subtype. Our study will enable a personalized treatment approach and assist in decisions on appropriate treatments for patients that will benefit while reducing over-treatment in patients who will not.  

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Lead: Dr. Michael Anglesio

Project: Precision Medicine for ENOC

Up until recently, researchers have believed that genetic mutations that control critical cell functions were exclusively linked to onset and progression of cancer. Our group, and others, recently showed that normal tissue can survive with cancer-associated mutations, without becoming cancer or exhibiting any obvious changes under the microscope. Cells in the uterus seem to naturally acquire these mutations over time. Mutations can appear early in life, with ~30% of individuals having a detectable mutation in their uterus at the age of 20 and up to 80% by menopause, without any microscopic signs of abnormality. We aim to better understand what this may mean for an individual’s reproductive and general health. 

 

Lead: Dr. Michael Anglesio​​

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Health and Aging

Endometriosis-associated ovarian cancer: Understanding which patients are at high risk

Endometriosis is a common chronic condition characterized by lesions resembling uterine 

tissue found outside the uterus. It affects 10% of women (and other people with uteruses) and carries a 2 to 4-fold increased risk of two types of ovarian cancer, herein referred to as endometriosis-associated ovarian cancer.

 

Research examining endometriosis-associated ovarian cancer has historically relied on a self-reported or clinical diagnosis of endometriosis, however the best diagnostic test for endometriosis is a pathologic diagnosis, made under a microscope. We do not have enough information on how common endometriosis treatments impact risk for endometriosis-associated ovarian cancer. There is also a suggestion that endometriosis will take on atypical features, which can be identified by specialized gynecologic pathologists in the laboratory, prior to becoming cancer. However, this diagnosis differs across different pathologists, thus we need an objective way to identify endometriosis that is likely to become cancer. If we can identify objective tests that will indicate when endometriosis is likely to become cancer, we can intervene before cancer ever develops.

 

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ENOC whos at risk
Detectr study

  High-throughput Epigenomic Mapping of Regulatory Elements in Ovarian Cancer at Basepair Resolution

Ovarian Cancer is the deadliest gynecological cancer in the US. It consists of several subtypes, each biologically distinct with different clinical challenges. Two of these subtypes are clear-cell ovarian cancer (CCOC) and endometrioid ovarian cancer (ENOC).

 

We observed that during the different phases of the menstrual cycle, the two subtypes resemble normal endometrial cells. The cell type of where the accumulation of mutation occurs that cause cancer is often looked at when determining subtype. On the contrary, CCOC and ENOC both arise from the same cell of origin and share common genetic mutations yet demonstrate different cellular and treatment (or clinical) behavior. CCOC and ENOC highlight the importance of exploring the varying cellular states, rather than just looking at cellular types.

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This project aims to examine the biological regulation of individual cell variations in human ovarian cancer samples.

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Lead: Shen Lab

Epigenomic Mapping

Stability of Molecular Subtype Testing in High-Grade Serous Ovarian Carcinomas from Neoadjuvant Treated Patient

Endometriosis Projects

Around 10% of reproductive-age women have endometriosis, although the prevalence is thought to differ by ancestry, with rates the highest in Asians where around 15% of women are affected. The molecular drivers of this common chronic gynecologic condition are poorly understood, particularly in non-Whites. Endometriosis is a major cause of pain and infertility in women, is associated with significant financial burden, and multiple comorbidities including pain syndromes, inflammatory and immune conditions, anxiety, and depression. Endometriosis lesions often harbour mutations in cancer-associated genes, but the consequences of these mutations are poorly understood.

 

The goal of this project is to catalogue the spectrum of somatic mutations in endometriosis across White, Asian, Black, and Hispanic women and to identify therapeutic opportunities associated with specific mutations.  

Genes and pathways we discover to be associated with somatic mutation of genes in endometriosis represent novel opportunities for diagnosis and personalized treatment based on the specific landscape of a woman’s disease. 

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Co-Leads: Anglesio Lab & Lawrenson Lab

Functional genemic ethinicity

Surgery for Endometriosis: who gets better and who does not? 

Endometriosis affects ~1 million individuals in Canada. It is defined as tissue, which resembles tissue from inside the uterus (womb), growing outside of the uterus in other parts of the body. Endometriosis is associated with pelvic pain (including pain with sexual activity), infertility, and complications during pregnancy. It accounts for approximately $2 billion in annual costs to Canadian society, primarily due to the impact on healthcare costs and work/productivity. Standard treatments for endometriosis are hormonal medication and surgery. However, up to half of patients will require a repeat surgery (re-operation) within 5 years of an initial surgery. Little is known about which patients respond well to surgery in the long-term, and which patients do not and experience persistent symptoms.

We will examine which factors predict response after surgery for endometriosis. These include clinical and biomarker factors that measure aspects of the nervous system. We will then develop a tool to help patients and surgeons make a decision about whether to operate or not. This tool will improve the pre-operative counselling of patients with endometriosis about potential future outcomes. The goal is to avoid unnecessary surgeries and to provide precision surgical care for people with endometriosis.

 

Lead: Yong Lab 

Surgery, who gets it

This project is focused on characterizing the impacts of the COVID-19 pandemic on virtual, surgical, as well as multidisciplinary care for individuals living with endometriosis and chronic pelvic pain. Data from the Endometriosis Pelvic Pain Interdisciplinary Cohort (EPPIC) Registry will be used to compare patient outcomes before and during the pandemic, who have had virtual or virtual and in-person visits. This may help determine the efficacy of virtual care and better inform care practices during a pandemic.  

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Lead: Yong Lab

Chronic pelvic pain
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