FOXA2 in cancer: from fundamental biology to clinical translation

Forkhead box protein A2 (FOXA2), a member of the forkhead box (FOX) transcription factor family, is essential for organ development and metabolic homeostasis. As a pioneer factor, it binds to condensed chromatin and facilitates the access of other transcription factors to DNA. Its dysregulation is a hallmark of numerous cancers, where it exhibits complex, context-dependent roles as either an oncogene or tumor suppressor, influencing these processes in a cancer type-specific manner. This review provides a comprehensive synthesis of FOXA2 biology, detailing its fundamental functions, the intricate molecular networks through which it governs malignant phenotypes across diverse tissue types, and its emerging translational potential. We systematically evaluate the promise of FOXA2 as a diagnostic and prognostic biomarker and discuss the development of novel therapeutic strategies aimed at targeting FOXA2 or its regulatory pathways. By integrating contemporary preclinical and clinical evidence, this review delineates the current landscape and future directions for leveraging FOXA2 in oncology, aiming to bridge foundational knowledge with clinical application for researchers and practitioners.