Melica Brodeur, MD

2024 Early Career Investigator Grant Recipient

Jewish General Hospital
Modulating chromatin remodeling as a strategy to reverse immune evasion in ovarian cancer

Project Summary
Ovarian cancer (OC) is the most lethal gynecological cancer. Immunotherapy, a treatment that helps the immune system fight cancer, has achieved remarkable responses in cancer types that were once fatal. Its successes have brought new hope to OC patients, however the latest OC clinical trials have shown overall disappointing responses with immune checkpoint blockade (ICB), the most common type of immunotherapy. 

The interaction between OC and immune cells is influenced by various factors that alter the immune response and contribute to disease progression. Our research team is studying how to target these factors to improve the treatment of OC. One particular target is the SWI/SNF complex, made up of proteins involved in modifying the structure of DNA. In our recent study, we discovered that inhibiting the function of this complex increases the ability of OC cells to be recognized by the immune system. Another protein target, called HDAC6, that makes DNA less accessible has also been shown, when its function is inhibited, to increase the expression of immune-related genes. 

Based on these findings, targeting both factors is a logical therapeutic strategy to sensitize OC to immunotherapy for a more effective response. Therefore, we propose in our study to combine HDAC6 and SWI/SNF inhibitors with ICB. This novel study may be used to overcome barriers to immunotherapy and help us reach our goal to improve outcomes for patients with OC.

Bio
Dr. Melica Nourmoussavi Brodeur is currently a postdoctoral research fellow at the Memorial Sloan Kettering Cancer Center under the mentorship of Drs Britta Weigelt and Dmitriy Zamarin. Her research interests involve uncovering potential molecular vulnerabilities in ovarian cancers using novel preclinical models to develop personalized approaches to ovarian cancer treatment. Dr. Brodeur is a trained Canadian gynecologic oncologist. She obtained her Doctorate of Medicine from McGill University in Montreal after which she completed her residency in Obstetrics & Gynecology at the University of British Columbia in Vancouver. She then completed a four-year training in the Gynecologic Oncology and the Clinician-Investigator Programs at the Université de Montréal during which she completed her Master’s degree in Biomedical Sciences. Under the direction of research supervisor Dr. Anne-Marie Mes-Masson, her thesis focused on the comparison and utility of ovarian cancer preclinical models for treatment response assessment. Her research endeavors have earned her awards to support her research training and work including a multi-phase clinician-scientist trainee bursary from the Fonds de recherche du Québec – Santé (FRQS), the Canadian Institutes of Health Research (CIHR) – Canada Graduate Scholarship – and research excellence bursaries from the Montreal Cancer Institute. She is also among the prestigious alumni of the NCI-funded AACR Molecular Biology in Clinical Oncology Workshop. With OCRA’s support, Dr. Brodeur is interested in understanding the mechanistic basis underlying the tumor-immune cell interactions in ovarian cancers with SWI/SNF gene alterations, in particular SMARCA4-altered cancers. These studies could highlight new therapeutic strategies for these subtypes of ovarian cancer.