Tajik Zahra, Ghafouri-Fard Soudeh
Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Eur J Med Res. 2025 Aug 18;30(1):758. doi: 10.1186/s40001-025-03045-w.
Paclitaxel remains a cornerstone of cancer therapy, yet resistance significantly limits its clinical efficacy. Emerging evidence implicates circular RNAs (circRNAs) as key regulators of paclitaxel resistance, offering potential biomarkers and therapeutic targets. This review synthesizes current knowledge on circRNA-mediated resistance mechanisms, categorizing their roles as promoters or suppressors of chemoresistance. We highlight two major pathways-miRNA sponging and protein interactions-through which circRNAs alter drug sensitivity. Moreover, we focus on enhancement of epithelial-mesenchymal transition and modulation of autophagy as two significant downstream pathways influenced by the established primary mechanisms. Notably, our analysis reveals context-dependent dualities, where certain circRNAs exert opposing effects in different cancers, underscoring the need for tissue-specific therapeutic strategies. Furthermore, we identify critical gaps in understanding circRNA regulatory networks and their clinical translatability. By evaluating circRNA signatures associated with paclitaxel response, this review proposes a framework for biomarker development and combination therapies to circumvent resistance. Our findings emphasize the urgency of functional studies and standardized profiling methods to harness circRNAs for personalized oncology.
紫杉醇仍然是癌症治疗的基石，然而耐药性显著限制了其临床疗效。新出现的证据表明，环状RNA（circRNA）是紫杉醇耐药性的关键调节因子，有望成为生物标志物和治疗靶点。本综述综合了目前关于circRNA介导的耐药机制的知识，将它们的作用分类为化疗耐药的促进因子或抑制因子。我们重点介绍了circRNA改变药物敏感性的两条主要途径——miRNA海绵作用和蛋白质相互作用。此外，我们关注上皮-间质转化的增强和自噬的调节，这是受既定主要机制影响的两个重要下游途径。值得注意的是，我们的分析揭示了circRNA在不同癌症中发挥相反作用的背景依赖性双重性，强调了组织特异性治疗策略的必要性。此外，我们还确定了在理解circRNA调控网络及其临床可转化性方面的关键差距。通过评估与紫杉醇反应相关的circRNA特征，本综述提出了一个生物标志物开发和联合治疗的框架，以规避耐药性。我们的研究结果强调了开展功能研究和标准化分析方法的紧迫性，以便利用circRNA实现个性化肿瘤治疗。
