Circulating extracellular vesicle DNA (EV-DNA) and cell-free DNA in ovarian cancer: pathological relevance and diagnostic applications

Ovarian cancer is one of the leading causes of gynecologic cancer-related mortality in women. However, a significant proportion of ovarian cancer cases are only detected at an advanced stage (III or IV) and are complicated to treat because of metastasis to the peritoneum. This challenge is compounded by vague symptoms and insufficient screening methods for early ovarian cancer detection. A promising solution is liquid biopsy, where the presence of biomarkers (proteins, lipids, and nucleic acids) associated with cancer is identified in the blood circulation. This approach facilitates the real-time monitoring of cancer progression and treatment effects in a non-invasive manner. This contrasts with traditional tumor biopsy, where only a small portion of the tumor is sampled, serial sampling of the tumor is impractical, or sometimes, tumor biopsy is not feasible. This review discusses the cell-free and extracellular vesicle components in blood, highlighting their DNA as a target in liquid biopsies for cancer diagnostics, with a specific emphasis on ovarian cancer. It also underscores the need for further research into the biological underpinnings and functional roles of these DNA fragments to integrate them into multi-omics approaches for detailed insights into tumor biology and treatment resistance in ovarian cancer.