Circular RNA-based liquid biopsy: a promising approach for monitoring drug resistance in cancer

Abstract

Drug resistance remains a significant challenge in achieving successful cancer treatment, often leading to disease recurrence and reduced patient survival. While traditional tissue biopsies provide valuable insights into tumor biology, they are invasive, infrequent, and may fail to capture the full complexity of tumor heterogeneity and dynamic molecular changes. In contrast, liquid biopsy has emerged as a minimally invasive, real-time approach for monitoring tumor evolution through the analysis of circulating biomarkers. Among these biomarkers, circular RNAs (circRNAs) - a distinct class of non-coding RNAs characterized by covalently closed-loop structures - have gained attention due to their remarkable stability, abundance in body fluids, and functional involvement in gene regulation. Increasing evidence supports the role of circRNAs in mediating drug resistance through mechanisms such as inhibition of apoptosis, epithelial-mesenchymal transition, autophagy, and drug efflux, largely via interactions with microRNAs or proteins. Advanced detection methods, including quantitative reverse transcription polymerase chain reaction, droplet digital polymerase chain reaction, and RNA sequencing, combined with computational tools, enable precise profiling of circRNAs in plasma or exosomes. CircRNA-based liquid biopsies offer a dynamic, non-invasive strategy for early detection of therapeutic resistance and may guide personalized treatment decisions. This review highlights the technological advancements, biological relevance, and clinical promise of circRNAs as circulating biomarkers, emphasizing their potential in precision oncology and future collaborative translational applications.

Keywords

Liquid biopsy / circular RNAs (circRNAs) / drug resistance / cancer biomarkers / non-invasive monitoring

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