Unravelling the role of extracellular vesicles in cervical cancer: Mechanisms of progression, resistance, and emerging therapeutic strategies

Abstract

Cervical cancer remains a significant global health challenge, particularly in its advanced stages, where treatment resistance complicates effective management. Extracellular vesicles (EVs) are crucial mediators of tumor progression and resistance, primarily through the transfer of miRNA cargo. In cervical cancer, specific miRNAs, including oncogenic miRNAs such as miR-21, miR-221-3p, miR-486-5p, and miR-92a-3p are upregulated in both cells and EVs, promoting proliferation, migration, epithelial-to-mesenchymal transition (EMT), and immune evasion—all of which contribute to therapy resistance and an aggressive tumor phenotype. Conversely, tumor-suppressive miRNAs, such as miR-122-5p, miR-100, and miR-142-3p, are selectively exported from cancer cells via EVs, suggesting a protective mechanism by which cancer cells eliminate these tumor suppressors. This review focuses on the role of oncogenic and tumor-suppressive miRNAs within EVs and their implications for cervical cancer progression and treatment resistance. Additionally, it examines the dynamic interactions between the tumor microenvironment (TME) and EV cargo, as well as emerging EV-based therapeutic strategies. These include the encapsulation of chemotherapeutic agents within EVs, the use of anti-miRs to silence oncogenic miRNAs, the delivery of tumor-suppressive miRNAs, the inhibition of EV release, and the targeting of downstream miRNA-regulated proteins. While miRNA-based therapies remain in the early stages, they hold significant promise for overcoming treatment resistance and improving cervical cancer outcomes.