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Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review
Artur Słomka1, Miroslaw Kornek2, William C Cho3
1Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-094 Bydgoszcz, Poland.
Abstract:
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.
Insights
Exosomes, specifically small extracellular vesicles (sEVs), deliver non-coding RNAs (ncRNAs) that significantly impact cancer chemotherapy resistance. Understanding these exosomal ncRNAs is crucial for developing novel cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Extracellular vesicles (EVs), particularly exosomes (small EVs or sEVs), play a critical role in cancer progression.
- Exosomal non-coding RNAs (ncRNAs) are key mediators in modulating cancer cell sensitivity to chemotherapy.
Purpose of the Study:
- To review the mechanisms by which exosomes influence chemoresistance in cancer cells.
- To highlight the role of exosomal ncRNAs in chemotherapy failure and potential therapeutic strategies.
Main Methods:
- Analysis of molecular mechanisms involving exosomal microRNAs (miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs).
- Review of cellular and animal model studies demonstrating the impact of exosomal ncRNAs on cancer cell proliferation, survival, metastasis, and apoptosis resistance.
- Examination of clinical data linking exosomal ncRNAs to chemotherapy failure.
Main Results:
- Exosomal ncRNAs contribute to chemoresistance through translational repression of anti-oncogenes (by miRs) and oncogenes (by lncRNAs and circRNAs).
- These ncRNAs promote cancer cell proliferation, survival, metastasis, and apoptosis resistance, leading to clinical chemotherapy failures.
- Evidence suggests exosomal ncRNAs may also overcome chemoresistance, though data are fragmented.
Conclusions:
- Exosomes, via ncRNAs, are significant modulators of cancer cell response to chemotherapy.
- Further research into exosomal ncRNA mechanisms is essential for developing innovative therapeutic approaches to combat chemotherapy resistance.
