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.

Extracellular vesicles (EVs) are nanovesicles secreted for intercellular communication with endosomal network regulating secretion of small EVs (or exosomes) that play roles in cancer progression. As an essential oncoprotein, Kirsten rat sarcoma virus (KRAS) is tightly regulated by its endosomal trafficking for membrane attachment. However, the crosstalk between KRAS and EVs has been scarcely discussed despite its endocytic association. An overview of the oncogenic role of KRAS focusing on its correlation with cancer-associated EVs should provide important clues for disease prognosis and inspire novel therapeutic approaches for treating KRAS mutant cancers. Therefore, this review summarizes the relevant studies that provide substantial evidence linking KRAS mutation to EVs and discusses the oncogenic implication from the aspects of biogenesis, cargo sorting, and release and uptake of the EVs.