Congratulations to Dr. Amal El-Naggar, Dr. Farhia Kabeer, and Dr. Bengul Gokbayrak on receiving the Carraressi Foundation Research Award! We would also like to congratulate Dr. Jennifer Pors on receiving the Division of Gynaecologic Oncology Research Award and Dr. Bozena Zdaniuk on receiving the Sumiko Kobayashi Marks Memorial Award.
Earlier this year, the GCI launched a combined grants funding competition to support gynecologic cancer research. One-time grants of up to $20,000 were awarded in this round of funding applications. These grants are designed to support early and mid-career researchers, provide critical review, with rapid turn-around and constructive feedback, and funding for proposals that may not be eligible to receive funding at the national level. This funding opportunity was open to all OVCARE, Division of Gynaecologic Oncology, Provincial Gyne-Tumour Group and Gynecologic Cancer Initiative members.
Carraressi Foundation Research Grant Recipients
Dr. Amal El-Naggar
Amal is a board-certified anatomic pathologist and is currently a Research Associate at the BC Cancer Research Institute working in the Huntsman lab. Her work focuses on conserved cell stress signaling pathways underlying metastatic dissemination and how it relates to human pathology and identifies novel targets for the treatment of cancer.
Project Title: Cystathionine gamma-lyase inhibitors in the treatment of clear cell ovarian cancer
Project Summary: Clear cell ovarian cancer (CCOC) is the second most common type of ovarian cancer and represents 5-11% of cases in North America and is significantly more common (up to 25% of cases) in Japan, with over 70% of patients present with metastasis at diagnosis. CCOC is inherently resistant to standard platinum/taxane chemotherapy. Late-stage CCOC has a worse prognosis than other ovarian cancer histotypes, underscoring the urgent need to identify and develop new therapeutics. An extensive body of evidence has demonstrated the crucial role of hypoxia oxidative stress in the pathogenesis of CCOC. Our group has previously shown that the cystathionine gamma-lyase (CTH) enzyme, a key enzyme in the transsulfuration pathway, is a marker of ciliated cells and CCOC of the uterus and ovary but not other subtypes of ovarian cancer. Recently, we found that CTH is crucial for stress adaptation and the metastatic spread of CCOC. Using AI-accelerated docking technology to virtually screen ZINC22 database of up to 40 billion commercial chemicals against CTH, we identified 233 promising candidates. This proposal aims to validate these compounds as effective CTH antagonists via screening in an array of wet lab experiments to select the lead compounds. This research could be the first to provide solid pre-clinical data to help establish the likelihood of success of targeting CTH in CCOC and will provide much- needed preliminary data essential for a larger research grant application.
Dr. Farhia Kabeer
Dr. Farhia Kabeer is a gynae surgeon from Pakistan. Her cancer research took off from MSc at McGill University studying the metastatic potential of breast cancer cells. Farhia’s PhD research encompassed the fields of cancer evolution and translational breast cancer research. Currently, Farhia is a post-doctoral fellow at OVCARE and her work focuses on high-grade serous ovarian cancer pre-clinical models to test novel combinations therapies.
Project Title: Developing patient derived xenograft models to study HER2 intratumoural heterogeneity in p53abn endometrial cancers
Project Summary: Endometrial cancer (EC) is the most common gynecologic cancer in Canada and can be classified into four subtypes based on different molecular features. The most aggressive subtype of EC is called p53 abnormal (p53abn). We urgently need therapeutic advances to improve outcomes for these patients as they currently have poor survival rates. A proportion of p53abn ECs have extra copies of the human epidermal growth factor 2 (HER2) gene, and a previous study in EC showed patients with HER2 positive tumours had improved outcomes with the use of a drug that targets the HER2 protein on tumour cells (anti-HER2 therapy). However, we have also found that only a small proportion of the tumour cells have extra copies of HER2, reflecting a process called ‘tumour heterogeneity’. We have recently developed patient derived xenograft (PDX) models to assess the significance of HER2 tumour heterogeneity in p53abn EC and assess response to anti-HER2 therapy using different HER2 positive tumour cut offs. However, the tumours that grew out in mice had no or very focal HER2 positivity, therefore, in this study we plan investigate the reason for this and refine our method of developing PDX models. We hope this study will determine cut- off for response to anti-HER2 therapy which could be used in future clinical trial design.
Dr. Bengul Gokbayrak
Dr. Bengul Gokbayrak is a postdoctoral fellow supervised by Dr. Yemin Wang. She earned her PhD in Molecular Biology from Koc University, Turkey, where she focused on identifying critical epigenetic modifiers in prostate cancer. During her PhD, Dr. Gokbayrak spent three years as a visiting research student at the Vancouver Prostate Centre. Currently, she is studying biomarkers and targetable proteins of rare gynecologic cancers at the BC Cancer Centre.
Project Title: Identifying targetable surface proteins of SMARCA4/2-mutant gynecologic cancers
Project Summary: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and dedifferentiated endometrial/ovarian cancer (DDEC/DDOC) are rare but highly aggressive types of gynecologic cancers with no effective treatment options available. Recent genomic and immunohistochemistry analyses have identified that the defective SWI/SNF chromatin remodeling complex, particularly the dual loss of SMARCA4 and SMARCA2 (SMARCA4/2), underlies the development of both SCCOHT and DDEC/DDOC. While potential synthetic lethal treatment options have been identified for these SMARCA4/2-deficient gynecologic cancers, their clinical outcome remains to be proven. To inform the development of alternative therapeutic strategies, our project aims to identify potential cell surface proteins whose inhibition will suppress tumour growth. To accomplish this goal, we will first conduct surfaceome profiling on frozen patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) tumours. By comparing the surfaceome profiles of SCCOHT and DDEC to that of mixtures of a panel of cancer cell lines from various tissue types, we aim to identify cell surface proteins unique and/or highly abundant to SCCOHT and/or DDEC. To address whether the prioritized signature cell surface proteins of SCCOHT and DDEC will be essential for their growth, we will generate a focused CRISPR/Cas9 library and perform in vivo drop-out screen using both CDX and PDX models. This pilot study will yield a number of screen hits with high translational potential that will support a grant application to the national level of funding competitions for funds to support future validation, mechanistic, and therapeutic development studies.
Division of Gynaecologic Oncology Research Award
Dr. Jennifer Pors
Dr. Jennifer Pors is a pathologist and Clinical Assistant Professor at BC Cancer and the University of British Columbia. She completed medical school at McGill University, followed by residency training in Anatomical Pathology at the University of British Columbia, and a fellowship in gynecologic pathology at Stanford University.
Project Title: The Spectrum of Estrogen Receptor Expression in Endometrial Adenocarcinoma of No Specific Molecular Profile
Project Summary: Endometrial cancer, cancer of the inner lining of the uterus, is the most common gynecologic cancer. Endometrial cancers are divided into four groups based on their molecular features. The largest and most diverse group is the No Specific Molecular Profile (NSMP) group. Estrogen receptor (ER) is a hormone receptor found in endometrial cancer. Research has shown that loss of Estrogen receptor in endometrial cancers identifies patients at risk of dying or having their cancer come back in the NSMP group. While Estrogen receptor plays an important role in endometrial cancer, what constitutes an ER negative endometrial cancer is unclear. In the absence of strong data, many different definitions of negative ER have been proposed. Using a large group of endometrial cancers diagnosed on our service, our goal is to determine a clinically relevant cut-off for ER in endometrial cancer.
Sumiko Kobayashi Marks Memorial Research Award
Dr. Bozena Zdaniuk
Dr. Bozena Zdaniuk has been a Research Associate in the UBC Department of Obstetrics and Gynaecology for seven years working at the Sexual Health Research Lab. She has been involved in all aspects of design and analysis of multiple clinical trials of treatments for sexual dysfunction, including those for cancer survivors. She has mentored numerous undergraduate and graduate students as well as post-doctoral trainees and is excited to be involved in this GCI funded project which seeks to disseminate the findings from a recent study exploring the experiences of gynaecologic cancer survivors who worked through an online sexual health intervention, eSense. She will receive ongoing mentorship from Dr. Lori Brotto over the course of this project.
Project Title: #SexAfterCancer: Sharing Knowledge About a Digital Health Tool to Address Sexual Difficulties After Gynecologic Cancer
Project Summary: It is well known that sexual difficulties are common after treatment of gynecologic cancer. However, there are very few effective and accessible treatments to address these concerns, leaving survivors to suffer in silence with sometimes longstanding sexual health issues. Over the past four years, our team has developed an online digital health tool that delivers two forms of psychological treatment— mindfulness and cognitive behavioural therapy—to treat sexual difficulties. We have shown in a large study of women with low sexual desire that this program, called eSense, is feasible, satisfying to users, and effective. More recently, we have worked with a group of gynecologic cancer survivors to adapt eSense to the specific sexual health issues that arise after cancer treatment. A group of survivors worked through eSense and provided both interview as well as questionnaire feedback on how to adapt eSense to eSense-Cancer. The goal of the present application is to use targeted messaging (via social media to survivor groups) to share the findings, and to engage a larger group of gynecologic cancer survivors who will (1) participate in the next phase of testing eSense-Cancer; (2) inform the next steps of this research, whether a larger clinical trial or a study evaluating implementation of eSense-Cancer at cancer centres; and (3) a broader awareness raising campaign designed to inform survivors about the common types of sexual difficulties they may experience after treatment.