During the past decade, liquid biopsy-related publications have increased exponentially, demonstrating the great potential of screening body fluids for diagnosis, monitoring, and prediction of therapy response in cancer patients. Next to well-established, cancer-associated analytes in the bloodstream, such as circulating tumor cells and cell-free DNA, an increasing number of studies have highlighted extracellular vesicles (EVs) as a promising source of novel tumor biomarkers. In this review, we discuss the advantages, limitations, and challenges of using EVs as cancer biomarkers, with a special focus on solid tumors.

Extracellular vesicles (EVs) are secreted by all living cells and are ubiquitous in every human body fluid. They are quite heterogeneous with regard to biogenesis, size, and composition, yet always reflect their parental cells with their cell-of-origin specific cargo loading. Since numerous studies have demonstrated that EV-associated proteins, nucleic acids, lipids, and metabolites can represent malignant phenotypes in cancer patients, EVs are increasingly being discussed as valuable carriers of cancer biomarkers in liquid biopsy samples. However, the lack of standardized and clinically feasible protocols for EV purification and characterization still limits the applicability of EV-based cancer biomarker analysis. This review first provides an overview of current EV isolation and characterization techniques that can be used to exploit patient-derived body fluids for biomarker quantification assays. Secondly, it outlines promising tumor-specific EV biomarkers relevant for cancer diagnosis, disease monitoring, and the prediction of cancer progression and therapy resistance. Finally, we summarize the advantages and current limitations of using EVs in liquid biopsy with a prospective view on strategies for the ongoing clinical implementation of EV-based biomarker screenings.