Exosomal microRNAs as Potential Biomarkers in Castration-resistant Prostate Cancer

Abstract

Castration-resistant prostate cancer (CRPC) develops as metastatic prostate cancer inevitably progresses and becomes resistant to treatment targeting the androgen signaling axis; CRPC represents the final stage of the disease, with a median survival of less than 2 yr. Although CRPC remains incurable, a number of treatment alternatives that yield modest prolongation of life have been developed and approved by the US Food and Drug Administration (FDA) during the last fewyears. These alternatives include selective adrenal inhibitors, androgen receptor signaling inhibitors, novel immune compounds, and less toxic radionuclides. However, progression towardsmore personalized treatment strategies is hamperedby the lack of easilymeasured reliable biomarkers predicting response to therapy and survival. In this issue of European Urology, Huang et al. [1] attempt to address this issue. They investigated the prognostic potential of microRNAs (miRNAs) within exosomes in circulation, and propose that twomiRNAs, miR-375 andmiR-1290, can serve as prognostic biomarkers for CRPC. ThemiRNAs identified by Huang et al. were derived from exosomes in the blood circulation; extensive attention is now focusing on these vesicles as a source of biomarkers because their contents resemble those of the cell of origin. In 2008, Skog et al. [2] showed that the miRNA content of extracellular vesicles reflects the miRNA expression profile of the cells they originated from; however, it should be noted that the miRNA content of exosomes is not an uncorrupted sample of the contents of the parental cells. When investigating the content of plasma-derived exosomes (or extracellular vesicles), Huang et al. [1] found that maturemiRNAswere themost common RNA species. This is