Grant: Project Grant

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but very aggressive type of ovarian cancer affecting young women. Its rarity has hampered the development of effective treatments. In 2014, several groups, including ours, discovered that SCCOHT is almost always caused by mutations in the gene SMARCA4. Our goal is to improve outcomes for women affected by this devastating cancer by providing new potential treatment strategies to treat SCCOHT. Part of our research strategy focuses on repurposing drugs already approved for other cancer types to treat SCCOHT. This approach can greatly facilitate clinical studies by bypassing drug development and safety testing. We recently found that SCCOHT cells are highly sensitive to a type of chemotherapy agents called CDK4/6 inhibitors, which are currently approved to treat breast cancer. This already led to a clinical study testing these inhibitors to treat SMARCA4-mutated cancers. Our research results suggest that SCCOHT cells are also sensitive to PARP inhibitors, also approved in Canada to treat another ovarian cancer subtype. In this project, we will fully validate PARP inhibitors as potential treatment for SCCOHT using a variety of model systems, including cell culture, mouse preclinical models, and patient tumor samples. As with all single-agent cancer therapies, drug resistance is expected to eventually arise in patients. To pre-empt this, we will use powerful genetic tools to identify the mechanisms at work in resistance development as well as identify novel drug targets in SCCOHT to develop secondary treatments or combination therapies to overcome resistance.