Exosomes: their role and therapeutic potential in overcoming drug resistance of gastrointestinal cancers

Abstract

Gastrointestinal cancers are prevalent malignant neoplasms in clinical medicine. The development of drug resistance in gastrointestinal cancers result in tumor recurrence and metastasis and greatly diminish the efficacy of treatment. Exosomes, as the shuttle of intercellular molecular cargoes in tumor micro-environment, secreted from tumor and stromal cells mediate drug resistance by regulating epithelial-mesenchymal transition, drug efflux, stem-like phenotype and cell metabolism. Meanwhile, exosomes have already received tremendous attention in biomedical study as potential drug resistant biomarkers as well as treatment strategy in gastrointestinal cancers. Primary challenge to implement this potential is the ability to obtain high-grade exosomes efficiently; however, exosomes lack standard protocols for their processing and characterization. Furthermore, this field suffers from insufficient standardized reference materials and workflow for purification, detection and analysis of exosomes with defined biological properties. This review summarize the unique biogenesis, composition and novel detection methods of exosomes and informed the underlying correlation between exosomes and drug resistance of gastrointestinal cancers. Moreover, the clinical applications of exosomes are also summarized, might providing novel therapy for the individual treatment of gastrointestinal cancers.

Keywords: biological function; clinical application; drug resistance; exosomes; gastrointestinal cancer.

Figure 1

Biogenesis and composition of exosomes. The process of plasma membrane budding inward generates early endosomes. These endosomes are transformed into MVBs after sequestering specific cargos. Finally, the ILVs inside the MVBs are released outside the cell as exosomes. Exosomes contain various nucleic acids, proteins, and lipids, each with specific function. By Figdraw.

Figure 2

Microfluidics technologies for exosomes separation and detection flowchart. The figure shows the common methods for exosome isolation and detection based on microfluidics, and lists the respective advantages and disadvantages of each method.

Figure 3

Functional role of exosome contents in GI cancer drug resistance. Exosomal differential proteins and nucleic acids from different cells play an important role in the reversal of drug resistance, providing favorable conditions for further promoting individualized treatment of GI cancer. By Figdraw.

Figure 4

Potential Clinical Applications of Exosomes in GI Cancer drug resistance. Targeted inhibition of oncogenic exosomes through gene editing and pharmacological inhibitors and scavenging techniques. Delivery of therapeutic RNA or small molecule drugs to tumor cells via exosomes. Exosomes from various cells function as vaccines to activate anti-tumor immune responses. By Figdraw.