Unravelling the Significance of Extracellular Vesicle‐Associated DNA in Cancer Biology and Its Potential Clinical Applications

ABSTRACT Extracellular vesicles (EVs) play a key role in cell‐to‐cell communication and have drawn significant attention due to their potential clinical applications. However, much remains to be understood about the biology of EV‐associated DNA (EV‐DNA). EV‐DNA is actively released by both normal and malignant cells and consists of diverse fragments with varying structures. Because EV‐DNA spans the entire genome of cells from which it originates, it continues to be attractive as a biomarker for cancer diagnosis and monitoring. Further, EV‐DNA delivery can alter the function of recipient cells by interfering with cytoplasmic DNA sensor pathways. This review explores the biology and significance of EV‐DNA, including its topology and fragmentomics features, modality of association with EVs, packaging mechanisms, and potential functions. It also emphasizes the specificity of vesicular DNA in identifying genetic and epigenetic changes in cancer. Additionally, it delves into the impact of EV‐DNA on cellular behaviour and its potential use as a therapeutic target in cancer. The review discusses new insights into EV‐DNA biology and provides perspectives and alternatives to address the challenges and concerns for future EV‐DNA studies.