The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends

Abstract

Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed. Graphical Abstract

Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases

“…MEVs, characterized by a bilayer lipid membrane, facilitate easy crossing of the blood–brain barrier and cell membranes, ensuring the targeted delivery of cargo. Oral administration of MEVs was found to be stable in the gastrointestinal tract and demonstrated effectiveness in reducing the primary tumor burden in mouse models of CRC and breast cancer [ 160 , 161 , 162 ].…”

“…PDAC cell death via clathrin-mediated endocytosis [149,150] Engineered small EVs with high CD47 expression and c(RGDyC) modification to deliver short RNAi against YTHDF1: a novel therapeutic strategy for GC via epigenetic and immune regulation [155,166] colon IBD EVs released by MSCs and loaded with miR-146: a new strategy in the treatment of IBD in mouse models [126] EVs and bacteria-derived membrane vesicles (OMVs) derived from normal feces: restore the intestinal barrier in IBD subjects [38,127,128,167] Exo containing PSMA7 derived from saliva: an important protein biomarker for IBD [168] CRC Folic acid-modified exo-liposome hybrid nanoparticles loaded with ALKBH5 mRNA: a novel therapeutic strategy for CRC [156] EVs derived from CT26 and loaded with miR-34a mimics: a new strategy for CRC gene therapy in mouse model [159] EVs derived from milk: a reduction in primary tumor burden in mouse models of CRC and breast cancer [161,162] Exosomes secreted from HEK293T transfected with Her2-mCherry plasmid and loaded with both 5-FU and miR-21i: reversing the drug resistance in CRC cells [164,165] Exosomes secreted from MSCs modified with 5TR1 or with magnetic nanoparticles, folic acid, and DOXO: the inhibition of CRC growth in mouse models [151][152][153][154]…”

Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors

“…The progress of CRC is related to various factors such as a high-fat diet, low dietary fiber intake, obesity, and smoking (14,15), and the clinical manifestations are usually characterized by abdominal pain, abdominal distension, intestinal obstruction, blood in the stools, and emaciation without any obvious triggers (16). Treatment modalities for CRC include surgery, chemotherapy, radiotherapy, and targeted therapy (17,18). Hepatocellular carcinoma (HCC) can be divided into primary HCC and secondary HCC.…”

Precision Oncology: Circulating Microvesicles as New Biomarkers in a Very Early Stage of Colorectal Cancer

“…The prevention and treatment of colorectal cancer (CRC) is a global health challenge since CRC ranks as the second leading cause of cancer-related mortality [20]. Recent studies highlight the importance of microvesicles as biomarkers for the early detection of CRC [21], prognosis, and the prediction of response to therapy [22,23].…”