An update on extracellular vesicles in multiple myeloma: a focus on their role in cell-to-cell cross-talk and as potential liquid biopsy biomarkers.

INTRODUCTION: Multiple myeloma (MM) is characterized by a clonal proliferation of neoplastic plasma cells (PCs) in bone marrow (BM) and the interplay between MM PCs and the BM microenvironment, which plays a relevant role in its pathogenesis. In this important cross-talk, extracellular vesicles (EVs) are active. EVs, including small and medium/large EVs, are lipid bi-layer particles released in circulation by normal and neoplastic cells. A selected cargo of lipids, proteins, and nucleic acids is loaded into EVs, and delivered locally and to distant sites, thus influencing the physiology of recipient cells. In the "liquid biopsy" context, EVs can be isolated from human biofluids proving to be powerful markers in cancer. Areas covered: Here, we summarize the recent advances on EVs in MM field. Expert opinion: EVs from MM PCs: i) enhance malignant cell proliferation and aggressiveness through an autocrine loop; ii) are able to transfer drug resistance in sensitive-drug cells; iii) stimulate angiogenesis; iv) increase the activity of osteoclasts; and v) have immuno-suppressive effects. In addition, EVs from MM stromal cells also promote MM cell proliferation and drug resistance. Finally, we underline the importance of EVs as MM potential biomarkers in "cancer liquid biopsy" and as a potential new therapeutic target.