Abstract IA008: Discovery of fitness fingerprints and flower monoclonal ab therapy in ovarian cancer

Abstract Merging evidence suggests that cellular fitness competition between malignant cells and the tumor microenvironment (TME) dictates tumor progression. We recently identified Flower isoforms as molecular “fitness fingerprints,” where cancer cells expressing Flower-Win gain dominance over surrounding cells marked with Flower-Lose. In this study, we uncover that loss of stromal fitness is not an inherent trait but rather a cancer-driven event. Tumor cells secrete a specific long non-coding RNA, Tu-Stroma, via exosomes, which reprograms splicing of the Flower locus in TME cells, enforcing Flower-Lose expression and thereby reducing stromal competitiveness. This cancer-induced shift establishes a permissive niche that accelerates growth, metastatic dissemination, and ultimately shapes host survival in ovarian cancer. Therapeutically, blockade of Flower using a fully humanized monoclonal antibody (Aenya) markedly suppressed tumor expansion and peritoneal spread in patient-derived xenograft models. Importantly, prophylactic administration preserved the integrity of intraperitoneal organs even in the presence of highly aggressive tumor cells. These findings highlight a previously unrecognized mechanism of cancer-driven stromal takeover and establish Flower as a first-in-class therapeutic target with broad implications for preventing metastatic colonization. Citation Format: Rajan G. Gogna. Discovery of fitness fingerprints and flower monoclonal ab therapy in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr IA008.