Soleimani Alireza, 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.
Mol Biol Rep. 2025 Aug 6;52(1):796. doi: 10.1007/s11033-025-10908-2.
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of several malignancies, including both hematological malignancies and solid tumors. However, the development of resistance to TKIs is a key clinical challenge, resulting in disease progression and therapeutic failure. CircRNAs, a class of covalently closed non-coding RNA molecules, are now recognized as key players in this process. Dysregulation of circRNAs leads to TKI resistance by influencing key pathways such as apoptosis, autophagy, epithelial-mesenchymal transition, and alternative kinase activation. While challenges in clinical translation persist, advances in RNA-targeted technologies and detailed mechanistic assays are expected to enable application of circRNA-based interventions to overcome TKI resistance. This review summarizes the current knowledge on circRNAs in the context of TKI resistance in solid tumors, highlighting their functional roles, fundamental mechanisms, and possible clinical applications in bypassing drug resistance and refining cancer therapy outcomes.
酪氨酸激酶抑制剂（TKIs）彻底改变了多种恶性肿瘤的治疗方式，包括血液系统恶性肿瘤和实体瘤。然而，对TKIs产生耐药性是一个关键的临床挑战，会导致疾病进展和治疗失败。环状RNA（circRNAs）是一类共价闭合的非编码RNA分子，现在被认为是这一过程中的关键因素。环状RNA的失调通过影响细胞凋亡、自噬、上皮-间质转化和替代激酶激活等关键途径导致对TKIs的耐药性。虽然临床转化仍面临挑战，但基于RNA的技术进步和详细的机制分析有望使基于环状RNA的干预措施得以应用，以克服对TKIs的耐药性。本综述总结了目前关于实体瘤中环状RNA在TKIs耐药背景下的知识，突出了它们的功能作用、基本机制以及在绕过耐药性和改善癌症治疗结果方面可能的临床应用。
