Tumor microenvironment and biomarker innovation in ovarian cancer: mechanistic insights into immune evasion, angiogenesis, and therapeutic resistance
Ovarian cancer remains one of the most lethal gynecologic malignancies, largely because of late-stage diagnosis, extensive intratumoral heterogeneity, and the dynamic complexity of the tumor microenvironment (TME). Emerging evidence highlights the TME as a central orchestrator of immune evasion, angiogenic remodeling, and therapeutic resistance, which are three mechanistic pillars that critically shape disease progression and treatment outcomes. This narrative review synthesizes current mechanistic insights into how stromal, immune, and vascular components interact to promote tumor survival and metastasis. We examine the roles of immunosuppressive cell populations, cytokine networks, and checkpoint pathways in facilitating immune escape; delineate angiogenic drivers and endothelial-tumor crosstalk that sustain aberrant vascularization; and explore TME-mediated mechanisms that underlie chemoresistance, targeted therapy failure, and limited immunotherapy responsiveness. Furthermore, we evaluate recent advances in biomarker discovery, including the identification of circulating ncRNAs, exosomal signatures, spatial immune profiles, and TME-derived molecular indicators, which hold promise for improving early detection, prognostication, and therapeutic stratification. By integrating mechanistic biology with translational biomarker innovation, this review outlines a forward-looking framework for leveraging TME-informed diagnostics and therapeutics to enhance precision oncology in ovarian cancer.