Hypoxic regulation of extracellular vesicles: Implications for cancer therapy

Extracellular vesicles (EVs) play a pivotal role in intercellular communication and have been implicated in cancer progression. Hypoxia, a pervasive hallmark of cancer, is known to regulate EV biogenesis and function. Hypoxic EVs contain a specific set of proteins, nucleic acids, lipids, and metabolites, capable of reprogramming the biology and fate of recipient cells. Enhancing the intrinsic therapeutic efficacy of EVs can be achieved by strategically modifying their structure and contents. Moreover, the use of EVs as drug delivery vehicles holds great promise for cancer treatment. However, various hurdles must be overcome to enable their clinical application as cancer therapeutics. In this review, we aim to discuss the current knowledge on the hypoxic regulation of EVs. Additionally, we will describe the underlying mechanisms by which EVs contribute to cancer progression in hypoxia and outline the progress and limitations of hypoxia-related EV therapeutics for cancer.