Histotype and molecular subtype integration in epithelial ovarian cancer: implications for targeted treatment

Abstract

Ovarian cancer remains a major global health burden among women, ranking eighth in both cancer incidence and cancer mortality worldwide in 2024, with an estimated 330,731 new cases and 203,850 deaths. Epithelial ovarian cancer (EOC) accounts for more than 90% of ovarian cancers and comprises five major histological subtypes with distinct biological behavior, molecular alterations, and therapeutic vulnerabilities. However, most EOC histotypes continue to be managed primarily with surgery and platinum-based chemotherapy, underscoring the need to better define histotype-informed molecular targets and precision therapeutic strategies. This review summarizes the histological features, frequent molecular alterations, dysregulated signaling pathways, and clinically relevant protein-expression patterns across major EOC histotypes, with emphasis on their potential therapeutic implications. Representative clinical and preclinical evidence supporting histotype-specific targeted therapies is also discussed, with attention to differences in therapeutic actionability and evidence maturity. Building on this histotype-specific evidence, an integrated histotype-molecular therapeutic stratification framework covering five major EOC histotypes is proposed. By integrating histologic context with molecular profiling, this framework may help refine precision-guided therapeutic approaches and complement conventional management. Nevertheless, the clinical applicability and long-term benefits of therapies guided by this stratification framework remain to be confirmed in prospective studies.