Chemoresistance in cancer cells: exosomes as potential regulators of therapeutic tumor heterogeneity

Drug resistance in cancer cells remains a fundamental challenge. Be it nontargeted or targeted drugs, the presence of intrinsic or acquired cancer cell resistance remains a great obstacle in chemotherapy. Conventionally, a spectrum of cellular mechanisms defines drug resistance including overexpression of antiapoptotic proteins and drug efflux pumps, mutations in target and synergistic activation of prosurvival pathways in tumor cells. In addition to these well-studied routes, exosome-induced chemoresistance is emerging as a novel mechanism. Mechanistically, exosomes impart resistance by direct drug export, transport of drug efflux pumps and miRNAs exchange among cells. Moreover, exosome signaling creates 'therapeutic tumor heterogeneity' and favorably condition tumor microenvironment. Here, we discuss exosomes' role in chemoresistance and possibilities of developing novel therapeutic strategies.