The Dual Role of Circular Rnas in Paclitaxel Resistance: Insights Into Molecular Mechanisms and Clinical Implications Publisher Pubmed



Maghrebighojogh E ; Allela OQB ; Alfarttoosi KH ; Ghalib Taher S ; Alwan M ; Jasem Jawad M ; Mushtaq H ; Zareanshahraki M ; Gandomkar H
Source: Cell Cycle Published:2025

Abstract

Paclitaxel is a widely used chemotherapeutic agent that plays a vital role in the treatment of various cancers, including breast, ovarian, and lung cancers. Despite its success, the development of resistance significantly limits its long-term efficacy. Paclitaxel resistance involves a range of molecular mechanisms, including alterations in drug transport, mutations in β-tubulin, and activation of pro-survival signaling pathways. Recent studies have highlighted the crucial role of circular RNAs (circRNAs) in mediating paclitaxel resistance. CircRNAs are characterized by their stable, covalently closed structures, which protect them from exonuclease degradation. They regulate drug resistance through various mechanisms, including modulating transcription factors and influencing cellular processes such as apoptosis, immune response, and cancer stem cell dynamics by sponging microRNAs. This review focuses on the mechanisms by which circRNAs contribute to paclitaxel resistance and discusses their dual roles as both oncogenes and tumor suppressors. Furthermore, we explore the potential of circRNAs as novel therapeutic targets to overcome paclitaxel resistance. By targeting specific circRNAs or restoring tumor-suppressive circRNAs, it may be possible to enhance paclitaxel sensitivity and improve treatment outcomes. Future research is essential to further understand the role of circRNAs in paclitaxel resistance and to develop effective circRNA-targeted therapies for cancer treatment. © 2025 Elsevier B.V., All rights reserved.