From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research

Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which may in turn impact delivery, uptake and cargo function in recipient cells. A mechanistic understanding of exosome biology is therefore crucial to investigating exosomal function in complex biological systems and to the development of novel therapeutic approaches. Here, we outline the steps in exosome biogenesis, including endosome formation, MVB formation, cargo sorting and extracellular release, as well as exosome absorption, including targeting, interaction with recipient cells and the fate of internalized exosomes. In addition to providing a framework of exosome dynamics, we summarize current evidence on major pathways and regulatory mechanisms. We also highlight the various mechanisms observed in cancer and point out directions to improve study design in exosome biology. Further research is needed to illuminate the relationship between exosome biogenesis and function, which will aid the development of translational applications.