Extracellular Vesicle-Associated Epithelial–Mesenchymal Plasticity (EMP) as a Driver of Metastatic Evolution and Therapeutic Resistance in Ovarian Cancer

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.

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Publication Details

Journal
Cancers
Published
2026-11-09
DOI
https://doi.org/10.3390/cancers18213595
Primary Topic
Extracellular vesicles in disease
Type
article
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article

Extracellular Vesicle-Associated Epithelial–Mesenchymal Plasticity (EMP) as a Driver of Metastatic Evolution and Therapeutic Resistance in Ovarian Cancer

Farzana Alam, Ata Ullah, Julia N. Hibbard
Cancers
Extracellular vesicles in disease
article

Extracellular Vesicle-Associated Epithelial–Mesenchymal Plasticity (EMP) as a Driver of Metastatic Evolution and Therapeutic Resistance in Ovarian Cancer

Farzana Alam, Ata Ullah, Julia N. Hibbard
article en

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.

CancersVol. 18(21)
University of Utah (US)
Extracellular vesicles in disease
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