The role of extracellular vesicles in cell stress response and resistance to cancer therapy

Extracellular vesicles (EVs) are nanosized particles released by all cells that have been heralded as novel regulators of cell-to-cell communication. It is becoming increasingly clear that in response to a variety of stress conditions, cells employ EV-mediated intercellular communication to transmit a pro-survival message in the tumor microenvironment and beyond, supporting evasion of cell death and transmitting resistance to therapy. Understanding changes in EV cargo and secretion pattern during cell stress may uncover novel, targetable mechanisms underlying disease progression, metastasis and resistance to therapy. Further, the profile of EVs released into the circulation may provide a circulating biomarker predictive of response to therapy and indicative of microenvironmental conditions linked to disease progression, such as hypoxia. Continued progress in this exciting and rapidly expanding field of research will be dependent upon widespread adoption of transparent reporting standards and implementation of guidelines to establish a consensus on methods of EV isolation, characterisation and nomenclature employed.

Impact of anticancer therapies on extracellular vesicle EV content and release from the tumour microenvironment

Anti-cancer therapy stress causes EV release from tumour cells and associated stromal cells including cancer-associated fibroblasts (CAFs) (pink) and tumour-associated macrophages (TAMs) (Blue). The resultant EVs have altered content including various bioactives that can have a phenotypic impact in recipient cells. This figure was created using MindtheGraph. Abbreviations: epidermal growth factor receptor (EGFR), phosphorylated-EGFR (P-EGFR), genomic DNA (gDNA), breast cancer resistance protein (BCRP), multi-drug resistance protein 1 (MDR-1), P-glycoprotein (Pgp), short transient receptor potential channel 5 (TrpC5), cell-division cycle protein 20 (CDC20), long intergenic non-protein coding RNA, regulator of reprogramming (Linc-ROR) LincRNA-very low density lipoprotein receptor (lincRNA-VLDLR), cluster of differentiation 69 (CD69), natural killer group 2 membrane D (NKG2D), activating NK receptor NKp44 (NKp44), snail family transcriptional repressor 1 (SNAI1).