Small extracellular vesicles: Roles and clinical application in prostate cancer

Prostate cancer is a significant health problem in the United States. It is remarkably heterogenous, ranging from slow growing disease amenable to active surveillance to highly aggressive forms requiring active treatments. Therefore, being able to precisely determine the nature of disease and appropriately match patients to available and/or novel therapeutics is crucial to improve patients' overall outcome and quality of life. Recently small extracellular vesicles (sEVs), a subset of nanoscale membranous vesicles secreted by various cells, have emerged as important analytes for liquid biopsy and promising vehicles for drug delivery. sEVs contain various biomolecules such as genetic material, proteins, and lipids that recapitulate the characteristics and state of their donor cells. The application of existing and newly developed technologies has resulted in an increased depth of knowledge about biophysical structures, biogenesis, and functions of sEVs. In prostate cancer patients, tumor-derived sEVs can be isolated from biofluids, commonly urine and blood. They mediate intercellular signaling within the tumor microenvironment and distal organ-specific sites, supporting cancer initiation, progression, and metastasis. A mounting body of evidence suggests that sEV components can be potent biomarkers for prostate cancer diagnosis, prognosis, and prediction of disease progression and treatment response. Due to enhanced circulation stability and bio-barrier permeability, sEVs can be also used as effective drug delivery carriers to improve the efficacy and specificity of anti-tumor therapies. This review discusses recent studies on sEVs in prostate cancer and is focused on their role as biomarkers and drug delivery vehicles in the clinical management of prostate cancer.