Extracellular Vesicles in Colorectal Cancer: From Tumor Growth and Metastasis to Biomarkers and Nanomedications

SIMPLE SUMMARY: Almost all cell types produce extracellular vesicles that, according to their size, subcellular origin and release pathways, are mainly categorized as exosomes, ectosomes and apoptotic bodies. These vesicles exert a critical role in intercellular communication during physiological and pathological processes through the delivery of their cargo. Extracellular vesicles display the molecular features of the cells they originate and thus, they might serve as a basis for the noninvasive diagnosis of cancer or for patient follow-up using liquid biopsies. Furthermore, extracellular vesicles can be engineered for the selective and efficient delivery of molecular tracers and therapeutic agents for tumor imaging or treatment. This review provides an overview of the role of extracellular vesicles in the progression of colorectal cancers, in remodeling target tissue to facilitate premetastatic niche formation, their predictive value for the diagnosis and prognosis of colorectal cancer and the ongoing evaluations of their potential use as nanomedications. ABSTRACT: Colorectal cancer (CRC) is a leading public health concern due to its incidence and high mortality rates, highlighting the requirement of an early diagnosis. Evaluation of circulating extracellular vesicles (EVs) might constitute a noninvasive and reliable approach for CRC detection and for patient follow-up because EVs display the molecular features of the cells they originate. EVs are released by almost all cell types and are mainly categorized as exosomes originating from exocytosis of intraluminal vesicles from multivesicular bodies, ectosomes resulting from outward budding of the plasma membrane and apoptotic bodies’ ensuing cell shrinkage. These vesicles play a critical role in intercellular communications during physiological and pathological processes. They facilitate CRC progression and premetastatic niche formation, and they enable transfer of chemotherapy resistance to sensitive cells through the local or remote delivery of their lipid, nucleic acid and protein content. On another note, their stability in the bloodstream, their permeation in tissues and their sheltering of packaged material make engineered EVs suitable vectors for efficient delivery of tracers and therapeutic agents for tumor imaging or treatment. Here, we focus on the physiopathological role of EVs in CRCs, their value in the diagnosis and prognosis and ongoing investigations into therapeutic approaches.