Abstract 7763: FOXA1 in ovarian cancer: Therapeutic target and immunotherapy enhancer

Abstract OBJECTIVE This study aimed to elucidate the oncogenic role of FOXA1 (Forkhead Box A1) in ovarian cancer and to evaluate its potential as both a therapeutic target and a diagnostic biomarker. We further investigated whether FOXA1 inhibition could enhance responsiveness to immune checkpoint blockade and overcome chemoresistance. METHODS A total of 76 ovarian tissue samples were analyzed, including 9 normal, 34 benign, and 33 malignant specimens. Immunohistochemical (IHC) staining was performed to assess FOXA1 expression and its correlation with tumor stage. Functional studies were conducted using FOXA1 siRNA in SK-OV3 and HEYA8 cell lines. Changes in cell proliferation, migration, invasion, and wound-healing ability were evaluated following FOXA1 silencing. Quantitative RT-PCR was used to measure FOXA1 and epithelial-mesenchymal transition (EMT)-related gene expression. In addition, the effects of FOXA1 inhibition on sensitivity to carboplatin and the immune checkpoint inhibitor atezolizumab were assessed. RESULTS IHC analysis revealed significant differences in FOXA1 expression among normal, benign, and malignant tissues, with expression levels correlating with tumor stage. FOXA1 silencing significantly reduced cell proliferation and decreased migration and invasion by 60-80%. EMT-related genes were markedly downregulated after FOXA1 knockdown. Moreover, FOXA1 inhibition enhanced atezolizumab responsiveness and reduced carboplatin resistance in ovarian cancer cells. CONCLUSION FOXA1 acts as an oncogenic driver in ovarian cancer, promoting proliferation, invasion, and EMT activation. Its overexpression correlates with disease progression, supporting its role as a diagnostic and prognostic biomarker. Targeting FOXA1 may enhance immunotherapy efficacy and overcome chemoresistance in ovarian cancer. Citation Format: Taewan Kim, Baek MooJun, HyoWook Gil, Eunjung Yang, Kwangseock Kim, jaesung Ryu, Kong Hyejeong, Beamjun Park, Seob Jeon. FOXA1 in ovarian cancer: Therapeutic target and immunotherapy enhancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7763.