Chemotherapy resistance (CR) represents one of the most important barriers to effective oncological therapy and often leads to ineffective intervention and unfavorable clinical prognosis. Emerging studies have emphasized the vital significance of extracellular RNA (exRNA) in influencing CR. This thorough assessment intends to explore the multifaceted contributions of exRNA, such as exosomal RNA, microRNAs, long non-coding RNAs, and circular RNAs, to CR in cancer. We discuss the mechanisms by which exRNA facilitates drug resistance, such as modulating gene expression, influencing the tumor microenvironment, and facilitating intercellular communication. Furthermore, we examine the potential of exRNA as prognostic factor for determining oncology treatment efficacy and their emerging role as therapeutic targets. Diagnostic and prognostic applications of exRNA biomarkers are considered, alongside current methodologies for their detection and quantification. Additionally, we review recent advances in exRNA-targeted therapies, highlighting ongoing clinical trials and therapeutic strategies aimed at overcoming chemoresistance. Despite the promise of exRNA research, several challenges remain, including technical limitations and the biological complexity of exRNA networks. This review underscores the importance of continued investigation into exRNA biology and its therapeutic potential, which in the future may provide new avenues for cancer treatment and tailored medical strategies. By elucidating the role of exRNA in CR, this article aims to provide a comprehensive resource for researchers and clinicians seeking to improve the effectiveness of carcinoma management approaches.
Keywords: Biomarkers; Drug resistance; ExRNA-targeted therapy; Exosomal RNAs; Tumor microenvironment.
© 2025. The Author(s), under exclusive licence to Springer Nature B.V.