Context-dependent roles of HtrA2/Omi in ovarian cancer: mitochondrial apoptotic function linking platinum sensitivity and acquired chemoresistance-a narrative review.

BACKGROUND AND OBJECTIVE: Epithelial ovarian cancer often responds to platinum therapy but frequently relapses with acquired chemoresistance. HtrA2/Omi is a mitochondrial serine protease that can promote apoptosis after cytosolic release. This narrative review synthesizes ovarian-cancer-specific and mechanistic evidence and asks whether HtrA2/Omi is better understood as a static expression marker or as a stress-activated apoptotic effector linked to platinum response. METHODS: PubMed, Web of Science, Scopus, and reference lists were searched through April 30, 2026 and updated through June 25, 2026 using terms related to HtrA2/Omi, PRSS25, ovarian cancer, platinum resistance, apoptosis, X-linked inhibitor of apoptosis protein (XIAP), mitochondrial release, cytosolic release and invasion. A structured narrative approach was used because the ovarian HtrA2/Omi literature is limited, heterogeneous, and unsuitable for pooled quantitative synthesis. KEY CONTENT AND FINDINGS: This review proposes a two-layer model. Baseline HtrA2/Omi abundance is context dependent and varies with histotype, assay platform, treatment state, and compartment resolution. In contrast, under platinum or mitochondrial stress, cytosolic HtrA2/Omi release more consistently supports XIAP relief, caspase activation, apoptosis, and platinum sensitivity. Persistent post-treatment HtrA2/Omi loss may mark an apoptosis-deficient resistant state. CONCLUSIONS: HtrA2/Omi should not be framed as a simple oncogene or tumor suppressor in ovarian cancer. Its clearest value is as a candidate response-linked, compartment-aware marker of platinum-induced apoptotic competence. Clinical use requires longitudinal, histotype-stratified and microenvironment-aware validation before treatment selection.