Simple Summary
Ovarian cancer remains one of the deadliest cancers affecting women, largely because it is often diagnosed after it has already spread throughout the abdomen and become resistant to treatment. Researchers have traditionally explained this spread through a process called epithelial–mesenchymal transition, in which cancer cells become more mobile and invasive. However, growing evidence suggests that ovarian cancer cells more commonly exist in flexible intermediate states, known as epithelial–mesenchymal plasticity, that allow them to adapt to changing conditions and survive therapy. This review highlights the role of extracellular vesicles (EVs), a broad class of membrane-bound particles released by cells, including a subset known as exosomes, in promoting these adaptive states. EVs can carry proteins and genetic material between cells, influencing communication within the tumor environment. We discuss how EV-associated signaling may contribute to metastasis and treatment resistance and how EV-associated molecules may serve as future biomarkers and therapeutic targets. Understanding these processes could lead to improved strategies for detecting and treating ovarian cancer.
Abstract
Ovarian cancer remains a lethal gynecologic malignancy, with high-grade serous ovarian carcinoma (HGSOC) accounting for a large proportion of advanced-stage disease. HGSOC commonly disseminates across the peritoneal cavity, where malignant ascites contain tumour cells, stromal and immune cells, soluble mediators, and extracellular vesicles (EVs). Although epithelial–mesenchymal transition (EMT) has often been used to ex-plain invasive behaviour, tumour cells may occupy reversible hybrid epithelial/mesenchymal states rather than completing a uniform transition. This review synthesizes evidence linking EV-associated communication with epithelial–mesenchymal plasticity (EMP), peritoneal dissemination, and treatment resistance, with particular attention to the strength and context of the evidence. We distinguish endosome-derived exosomes from small EV (sEV) preparations whose biogenesis has not been established, and separate observational associations from functional experiments, animal-model findings, and clinical evidence. Our central contribution is an evidence-calibrated framework connecting EV biology, ascites-associated selection pressures, and dynamic cell states while identifying where causal mechanisms and clinical utility remain unproven. EV associated cargo and EV-targeting approaches are promising research directions, but neither biomarker performance nor therapeutic benefit should be considered clinically established without independent validation.