Grant: Project Grant

Treatment of ovarian cancer has remained largely unchanged for the last 50 years. Patients have not received the benefits of therapeutic advances seen in other cancer types-targeted therapies have been difficult to develop and current immunotherapies have proven largely ineffective. As such, disease management routinely involves surgery and extensive chemotherapy regimens. Initial response is often positive, but recurrence and the development of therapy-resistant disease is common. Our work uses cutting-edge molecular profiling strategies to better understand common features of the cancer cells comprising these tumours. We have found that, despite the complex genetic differences between tumours, ovarian cancer cells can adopt and transition between three distinct "states"-represented by unique molecular fingerprints. One of these states (dubbed "SecB"), while rare in untreated tumours, becomes prominent in chemotherapy-treated tumours and metastatic cells. The objective of this study is to determine whether these distinct states have distinct properties and implications for disease progression, and whether this SecB state can be therapeutically targeted to improve the response to chemotherapy and slow metastasis. To address this, we will use cell models derived directly from tumours to study the behaviour of these different subpopulations. We will also study the localization of these cells throughout tumours before and after treatment to better understand how these subpopulations may emerge. Finally, we have preliminary evidence to suggest that the SecB state may be particularly sensitive to an FDA-approved therapy not current used for ovarian cancer. We will test whether this can be used to selectively target this population. Together, we will explore the efficacy of new targeted strategies to improve treatment response and slow disease progression. Ultimately, we hope to provide more therapeutic options and improve outcomes for patients with this disease.