Molecular actions of exosomes and their theragnostics in colorectal cancer: current findings and limitations

Extracellular vesicles (EVs) are cell-released, membranous structures essential for intercellular communication. The biochemical compositions and physiological impacts of exosomes, lipid-bound, endosomal origin EVs, have been focused on, especially on the tumor-host interactions in a defined tumor microenvironment (TME). Despite recent progress in targeted therapy and cancer immunotherapy in colorectal cancer (CRC), cancer patients still suffer from distal metastasis and tumor relapse, suggesting unmet needs for biomarkers directing therapeutic interventions and predicting treatment responsiveness. As exosomes are indispensable for intercellular communication and high exosome abundance makes them feasible biomarker molecules, this review discusses exosome heterogeneity and how exosomes orchestrate the interplay among tumor cells, cancer stem cells (CSCs) and host cells, including stromal cells, endothelial cells and immunocytes, in the CRC TME. This review also discusses mechanisms for loading exosomal contents and potential exosomal DNA, RNA and protein biomarkers for early CRC detection. Finally, we summarize the diagnostic and therapeutic exosomes in clinical trials. We envision that detecting and targeting cancer-specific exosomes could provide therapeutic advances in developing personalized cancer medicine.