Extracellular vesicles in urological malignancies: an update

Extracellular vesicles (EVs) have an essential functional role in local tumour progression, metastatic spread and the emergence of drug resistance in bladder, kidney and prostate cancer. Thus, EVs could be diagnostic, prognostic and predictive biomarkers for these malignancies. Virtually all biomolecules (including DNA, mRNA, microRNA, long non-coding RNA, proteins and lipids) packaged into EVs have been tested as biomarkers in blood and urine samples. The results are very heterogeneous, but promising biomarker candidates have been identified. Differing methods of EV isolation, characterization and analysis of their content have been used owing to a lack of international consensus; hence, comparing study results is challenging. Furthermore, validation of potential biomarkers in independent cohorts or prospective trials has rarely been performed. Future efforts to establish EV-derived biomarkers need to adequately address these points. In addition, emerging technologies such as mass spectroscopy and chip-based approaches can identify surface markers specific for cancer-associated EVs and will enable specific separation from blood and urine EVs, which probably will improve their performance as biomarkers. Moreover, EVs could be harnessed as therapeutic drug delivery vehicles for precise and effective anticancer therapy. Here, Linxweiler and Junker provide an update on our understanding of the functional role of extracellular vesicles in urological malignancies and discuss their applicability as diagnostic, prognostic and predictive biomarkers in the three most prevalent urological cancers. Key points Extracellular vesicles (EVs) isolated from different body fluids reflect the molecular profile of their parental cells and are, therefore, a new class of biomarkers in liquid biopsies from patients with urological cancer. Biomarker studies are mainly focused on mRNAs and microRNAs as the most promising diagnostic tools using EVs in bladder, kidney and prostate cancer; data on prognostic and predictive EV markers are still limited. Comparability and reproducibility of published data is complicated because different isolation techniques have been used; in order to introduce EVs into clinical management, standardized techniques for routine isolation and characterization need to be defined. Identification of tumour-specific EV markers (such as prostate-specific membrane antigen in prostate cancer) will increase their diagnostic accuracy. EVs regulate communication b