Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

In recent years, tremendous progress has been made in understanding the roles of extracellular vesicles (EVs) in cancer. Thanks to advancements in molecular biology, it has been found that the fraction of EVs called exosomes or small EVs (sEVs) modulates the sensitivity of cancer cells to chemotherapeutic agents by delivering molecularly active non-coding RNAs (ncRNAs). An in-depth analysis shows that two main molecular mechanisms are involved in exosomal modified chemoresistance: (1) translational repression of anti-oncogenes by exosomal microRNAs (miRs) and (2) lack of translational repression of oncogenes by sponging of miRs through long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). At the cellular level, these processes increase the proliferation and survival of cancer cells and improve their ability to metastasize and resist apoptosis. In addition, studies in animal models have shown enhancing tumor size under the influence of exosomal ncRNAs. Ultimately, exosomal ncRNAs are responsible for clinically significant chemotherapy failures in patients with different types of cancer. Preliminary data have also revealed that exosomal ncRNAs can overcome chemotherapeutic agent resistance, but the results are thoroughly fragmented. This review presents how exosomes modulate the response of cancer cells to chemotherapeutic agents. Understanding how exosomes interfere with chemoresistance may become a milestone in developing new therapeutic options, but more data are still required.

Automated summary

Extracellular vesicles, particularly exosomes or small EVs (sEVs), have been found to play a significant role in modulating the sensitivity of cancer cells to chemotherapeutic agents through the delivery of non-coding RNAs (ncRNAs). The mechanisms involved include translational repression of anti-oncogenes by exosomal microRNAs (miRs) and lack of translational repression of oncogenes by sponging of miRs through long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These processes ultimately result in increased proliferation and survival of cancer cells, enhanced metastasis, and resistance to apoptosis, leading to chemotherapy failures in different types of cancer patients.