Bijaya Malla, Kathrin Zaugg, Erik Vassella, Daniel M. Aebersold, Alan Dal Pra

Despite current risk stratification systems using traditional clinicopathologic factors, many localized and locally advanced prostate cancers fail radical treatment (ie, radical prostatectomy, radiation therapy with or without androgen deprivation therapy). Therefore, a pressing need exists for enhanced methods of disease stratification through novel prognostic and predictive tools that can reliably be applied in clinical practice. Exosomes are 50- to 150-nm small vesicles released by cancer cells that reflect the genetic and nongenetic materials of parent cancer cells. Cancer cells can contain distinct sets of microRNA profiles, the expression of which can change owing to stress such as radiation therapy. These alterations or distinctions in contents allow exosomes to be used as prognostic and/or predictive biomarkers and to monitor the treatment response. Additionally, microRNAs have been shown to influence multiple processes in prostate tumorigenesis, including cell proliferation, induction of apoptosis, migration, oncogene inhibition, and radioresistance. Thus, comparative exosomal microRNA profiling at different levels could help portray tumor aggressiveness and response to radiation therapy. Although technical challenges persist in exosome isolation and characterization, recent improvements in microRNA profiling have evolved toward in-depth analyses of the exosomal cargo and its functions. We have reviewed the role of exosomes and exosomal microRNAs in biologic processes of prostate cancer progression and radiation therapy response, with a particular focus on the development of clinical assays for treatment personalization.