Probing extracellular vesicles promises early detection of ovarian cancer

The liquid biopsy is a promising strategy for advanced cancer management, allowing for minimally invasive and repeatable disease monitoring. In contrast, detecting early cancer through liquid biopsy is challenging due to the lack of specific biomarkers for early lesions and potentially low levels of these markers. Such challenges are evident with ovarian cancer, which is mostly asymptomatic until late and often incurable stages. Conventional blood testing (e.g., CA125) and imaging have failed to demonstrate survival advantages in a large, multi-year screening trial, underscoring the need for improved detection methods and informed marker selection. The new study by CSB investigators reports a systematic development of an extracellular-vesicle (EV)-based test for early cancer detection, focusing on high-grade serous ovarian carcinoma (HGSOC), the most common (75%) and lethal ovarian cancer subtype. The marker selection was based on emerging insights into HGSOC biology, notably that it arises from precursor lesions within the fallopian tube before spreading to ovarian and peritoneal surfaces. To identify fallopian tube-derived markers, the investigators established murine fallopian tube (mFT) cells with oncogenic mutations and performed proteomic analyses on mFT-derived EVs. The marker candidates were then evaluated with an orthotopic HGSOC animal model. In serially-drawn blood samples of tumor-bearing mice, mFT-EV markers increased with tumor initiation, supporting their potential use in early cancer detection. The investigators further validated EV markers in a pilot clinical study. Analysis of EVs demonstrated high diagnostic accuracy (0.95) in distinguishing between cancer and non-cancer cases, as well as the ability to differentiate between non-cancer, early-stage (I & II) HGSOC, and late-stage (III & IV) HGSOC. This approach, for the first time inaugurated in fallopian tube-derived EVs, has the potential to monitor women at high risk for ovarian cancer and enable intervention before the development of advanced disease. This work has been published in Advanced Science.