Extracellular vesicles as a promising biomarker resource in liquid biopsy for cancer

Liquid biopsy is a minimally invasive biopsy method that uses molecules in body fluids as biomarkers, and it has attracted attention as a new cancer therapy tool. Liquid biopsy has considerable clinical application potential, such as in early diagnosis, pathological condition monitoring, and tailored treatment development based on cancer biology and the predicted treatment response of individual patients. Extracellular vesicles (EVs) are lipid membranous vesicles released from almost all cell types, and they represent a novel liquid biopsy resource. EVs carry complex molecular cargoes, such as proteins, RNAs [e.g., mRNA and noncoding RNAs (microRNA, transfer RNA, circular RNA and long noncoding RNA)], and DNA fragments; these cargoes are delivered to recipient cells and serve as a cell-to-cell communication system. The molecular contents of EVs largely reflect the cell of origin and thus show cell-type specificity. In particular, cancer-derived EVs contain cancer-specific molecules expressed in parental cancer cells. Therefore, analysis of cancer-derived EVs might indicate the presence and nature of cancer. High-speed analytical technologies, such as mass spectrometry and high-throughput sequencing, have generated large data sets for EV cargoes that can be used to identify many candidate EV-associated biomarkers. Here, we will discuss the challenges and prospects of EV-based liquid biopsy compared to other biological resources (e.g., circulating tumor cells and cell-free DNA) and summarize the novel studies that have identified the remarkable potential of EVs as a cancer biomarker.