Abstract
With the ever-growing number of cancer deaths worldwide, researchers have been working hard to identify the key reasons behind the failure of cancer therapies so the efficacy of those therapies may be improved. Based on extensive research activities and observations done by researchers, chemoresistance has been identified as a major contributor to the drastic number of deaths among cancer patients. Several factors have been linked to formation of chemoresistance, such as chemotherapy drug efflux, immunosuppression, and epithelial-mesenchymal transition (EMT). Lately, increasing evidence has shed light on the role of extracellular vesicles (EVs) in the regulation of chemoresistance. However, there is limited research into the possibility that inhibiting EV release or uptake in cancer cells may curb chemoresistance, allowing chemotherapy drugs to target cancer cells without restriction. Prominent inhibitors of EV uptake and release in cancer cells have been compiled and contrasted in this review. This is in the hope of sparking greater interest in the field of EV-mediated chemoresistance, as well as to provide an overview of the field for fundamental and clinical research communities, particularly in the field of cancer resistance research. In-depth studies of EV-mediated chemoresistance and EV inhibitors in cancer cells would spur significant improvement in cancer treatments which are currently available.
Highlights
Chemoresistance, a state of cancer cells wherein chemotherapy drugs are ineffective against cancer progression, is a major challenge in cancer treatment
Many chemotherapy drugs function by targeting DNA replication, which prevents the growth of cancer cells and induces apoptosis – for example, cisplatin intercalates with double-stranded DNA whereas 5-fluorouracil inhibits DNA nucleotide synthesis (Chorowala et al, 2012)
The efficacy of using both GW4869 and manumycin A, neutral sphingomyelinase 2 (nSMase2) and ESCRTdependent inhibitors respectively, in the study proved that both endosomal sorting complexes required for transport (ESCRT)-independent and ESCRT-dependent activities are vital in exosome biogenesis in prostate cancer cell lines
Summary
Chemoresistance, a state of cancer cells wherein chemotherapy drugs are ineffective against cancer progression, is a major challenge in cancer treatment. This review will compile major drug inhibitors targeting specific mechanisms in the release and uptake of both exosomes and microvesicles (MVs) from cancer cells. An EV-related strategy against chemoresistance which holds promise includes inhibiting the biogenesis, release or uptake of EVs by cancer cells.
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