Abstract
Soon after the discovery of microRNAs over 15 years ago, a myriad of research groups around the world sought to develop clinical applications in breast cancer for these short, noncoding, regulatory RNAs. While little of this knowledge has translated into the clinic, the recent research explosion on cell-to-cell communication via exosomes and other extracellular vesicles has rekindled interest in microRNA-based clinical applications. microRNAs appear to be a preferential and important cargo of exosomes in mediating biological effects in recipient cells. This review highlights recent studies on the biology of exosomal microRNAs (exo-miRNAs) and discusses potential clinical applications. From a diagnostic perspective, circulating exo-miRNAs may represent breast cancer cell content and/or tumor microenvironmental reactions to cancer cell growth. Thus, serum or plasma analysis of exo-miRNAs could be useful for early disease detection or for monitoring treatment response and disease progression. From a therapeutic perspective, exo-miRNAs derived from different cell types have been implicated in supporting or restraining tumor growth, conferring drug resistance, and preparing the metastatic niche. Strategies to interfere with the loading or delivery of tumor-promoting exo-miRNAs or to replenish tumor-suppressive miRNAs via exosomal delivery are under investigation. These recent studies provide new hope and opportunities, but study design limitations and technical challenges will need to be overcome before seriously considering clinical application of exo-miRNAs.