New insights into extracellular vesicles in metastatic cancer: From mechanisms to diagnostics and targeted therapies.

Extracellular vesicles (EVs) play an indispensable role in a variety of physiological and pathological processes, including embryonic development, cellular migration, and malignant transformation of tumors. Tumor-derived exosomes (TDEs) have emerged as a key component of the tumor microenvironment (TME), intricately involved in tumor growth, vascular permeability, and pre-metastatic niche (PMN) formation. Consequently, TDEs encapsulate bioactive molecules in their lumen, facilitating their delivery to distant microenvironments and inducing the reprogramming of specific cell types to establish PMNs. This, in turn, endows cancer cells with robust capabilities for growth, metastasis, and chemoresistance. In this review, we consolidate current research elucidating the role of small EVs in cancer progression, with a particular focus on cancer metastasis, and their therapeutic potential. In addition, we review novel exosome-based methods, such as single-EV profiling, which aim to open new avenues for cancer research, diagnosis, and treatment.