High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic cancer and is now understood to arise primarily from serous tubal intraepithelial carcinomas (STICs) in the distal fallopian tubes, long before disease becomes clinically detectable. Although prophylactic removal of the fallopian tubes can prevent progression, this is not feasible for broad populations, creating an urgent need for molecular tools that can identify early STIC lesions and distinguish those with metastatic potential. Current diagnostic and risk-stratification methods lack the sensitivity and resolution needed to address this problem, leaving a significant gap in early intervention strategies.
This Early Detection Award will define the earliest steps of HGSOC development through single-cell and spatial characterization of incidental and cancer-associated STICs collected from a unique multi-institutional biobank. Using advanced tissue imaging and spatial transcriptomics, the investigators will map tumor intrinsic features and microenvironmental changes that accompany the transition from STIC to invasive cancer. These data will guide the discovery of secreted proteins enriched in STICs, with the most promising evaluated for use in highly sensitive, multiplexed plasma assays. Spatial and molecular features will also inform a tissue-based risk stratification framework to identify lesions likely to have already spread beyond the primary tumor site. This project is poised to deliver the first comprehensive molecular atlas of STIC biology, laying essential groundwork for a new clinical continuum that integrates early detection, personalized risk assessment, and informed decision-making around prophylactic surgery and surveillance. The long-term impact could be transformative for patients at risk of HGSOC, shifting care toward prevention and earlier intervention.