Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy

Simple Summary Gastrointestinal cancers originate in the digestive system and harbor distinct characteristics according to their site of origin. This review focusses on the role of small extracellular vesicles (sEVs, exosomes) in the progression, metastasis, and treatment of the main GI cancer entities, such as colorectal cancer, gastric cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma. In recent years, sEVs have gained increasing attention as important mediators of intercellular communication within the local tumor microenvironment, and also to distant metastatic niches. sEVs deliver bioactive cargos, like proteins, mRNA, and miRNAs, to reprogram target cells, promoting tumor growth, invasion, immune suppression, and metastasis to specific organs. Due to their presence in all biological fluids, sEVs are ideal biomarker platforms for multiplexing analysis. Furthermore, sEV engineering generated promising approaches for the use of sEV-based therapeutic nanovesicles in GI cancer treatment.Abstract Discovered in the late eighties, sEVs are small extracellular nanovesicles (30-150 nm diameter) that gained increasing attention due to their profound roles in cancer, immunology, and therapeutic approaches. They were initially described as cellular waste bins; however, in recent years, sEVs have become known as important mediators of intercellular communication. They are secreted from cells in substantial amounts and exert their influence on recipient cells by signaling through cell surface receptors or transferring cargos, such as proteins, RNAs, miRNAs, or lipids. A key role of sEVs in cancer is immune modulation, as well as pro-invasive signaling and formation of pre-metastatic niches. sEVs are ideal biomarker platforms, and can be engineered as drug carriers or anti-cancer vaccines. Thus, sEVs further provide novel avenues for cancer diagnosis and treatment. This review will focus on the role of sEVs in GI-oncology and delineate their functions in cancer progression, diagnosis, and therapeutic use.