Therapy resistance can arise within tumor cells because of genetic or phenotypic changes (intrinsic resistance), or it can be the result of an interaction with the tumor microenvironment (extrinsic resistance). Exosomes are membranous vesicles 40 to 100 nm in diameter constitutively released by almost all cell types, and mediate cell-to-cell communication by transferring mRNAs, miRNAs, DNAs and proteins causing extrinsic therapy resistance. They transfer therapy resistance by anti-apoptotic signalling, increased DNA-repair or delivering ABC transporters to drug sensitive cells. As functional mediators of tumor-stroma interaction and of epithelial to mesenchymal transition, exosomes also promote environment-mediated therapy resistance. Exosomes may be used in anticancer therapy exploiting their delivery function. They may effectively transfer anticancer drugs or RNAs in the context of gene therapy reducing immune stimulatory effects of these drugs and hydrophilic qualities facilitating crossing of cell membranes.
Exosomal cargo that mediates therapy resistance
Exosomes cause therapy resistance in the recipient cell by transporting DNA, RNA (micro RNA, short interfering RNA), lipids and proteins. They cause decreased apoptosis and anti tumor immunosurveillance and increased DNA repair and stemness in recipient cells. Furthermore they transport multidrug resistance (MDR) transporter to recipient cells or integrate them in reverse orientation in their membrane to decrease intra- and intercellular drug concentration