Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. Researchers from the Chittaranjan National Cancer Institute discuss all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer.

Exosomes in therapeutic approaches

Exosomes derived from DCs, APCs and stem cells can be utilized for immunotherapy, gene therapy, stem cell therapy and adjuvant therapy. Exosome based gene therapy is obtained by genetically engineered exosomes loaded with miRNA, siRNA and plasmids of interest. Stem cell or DC-derived exosomes can be implemented alone as vaccines and confer stem cell-based therapy or immunotherapy. The exosomes can also be utilized for drug delivery vectors by modifying them with drugs of interest. The DC-, APC- and stem cell-derived exosomes administered into the patient help in triggering immune response in combating cancer by targeting and regulating the mechanisms against which the exosomes are implemented. Abbreviations: APCs, antigen presenting cells; DCs, dendritic cells; miRNA, microRNA; siRNA, small interfering RNA.