The emerging roles of exosomes in anti-cancer drug resistance and tumor progression: An insight towards tumor-microenvironment interaction.

The tumor microenvironment (TME) is a complex network of cellular organization consisting of fibroblasts, adipocytes, pericytes, immune cells endothelial cells, and extracellular matrix proteins. Besides communicating with each other, tumor cells are also involved in the tumor stroma interaction. Presently, most of the studies have focused on the contribution of TME in supporting tumor growth through intercellular communication by physical contact between the cells or through paracrine signaling cascades of growth factors and cytokines. The crosstalk between the tumor and TME has a pivotal role in the development of anti-cancer drug resistance. Drug resistance, be it against targeted or non-targeted drugs, has emerged as a major hurdle in the successful therapeutic intervention of cancer. Among the several mechanisms involved in the development of the resistance to anti-cancer therapies, exosomes have recently come into the limelight. Exosomes are the nano-sized vesicles, originated from the endolysosomal compartments and have the inherent potential to shuttle diverse biomolecules like proteins, lipids, and nucleic acids to the recipient cells. There are also instances where the pharmacological compounds are transferred between the cells via exosomes. For instance, the transfer of the cargoes from the drug-resistant tumor cells immensely affects the recipient drug-sensitive cells in terms of their proliferation, survival, migration, and drug resistance. In this review, we have discussed multiple aspects of the exosome-mediated bidirectional interplay between tumor and TME. Furthermore, we have also emphasized the contribution of exosomes promoting drug resistance and therapeutic strategies to mitigate the exosome induced drug resistance as well.