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biomarker qualification pathway for circRNAs while ensuring compliance with clinical and ethical
standards [130] . In summary, advancing the field of circRNAs in liquid biopsy requires a multidisciplinary
strategy that integrates molecular biology, bioinformatics, clinical oncology, and regulatory science. With
sustained research investment and a strong translational focus, circRNAs hold the promise to transform
non-invasive cancer monitoring and the precision management of therapeutic resistance.
CONCLUSION
Combining liquid biopsy with circRNA research is a revolutionary way to monitor drug resistance in cancer.
circRNAs have a covalently closed-loop structure, making them highly stable in circulation and ideal
candidates for non-invasive biomarkers in real-time disease monitoring. Advances in molecular testing such
as qRT-PCR, ddPCR, and RNA seq have provided adequate sensitivity and specificity to detect circRNA
from plasma, serum, and exosomes. In this way, circRNA can be linked to specific resistance mechanisms
that include the regulation of apoptosis, autophagy, epithelial–mesenchymal transition, and drug efflux. By
assessing therapeutic responses, circRNA-based liquid biopsy can capture molecular changes, enabling
real-time interpretation of these dynamic events. Beyond this analytical purpose, liquid biopsy with
circRNAs can guide treatment decisions, enable early detection of resistance, and improve personalized
cancer care. Further standardization and clinical validation of such approaches are needed; nonetheless,
current evidence supports the potential of circulating circRNAs as future clinical tools in precision oncology.
DECLARATIONS
Acknowledgments
The authors thank BioRender.com (July 17, 2025) for assistance with graphics. Singh DD acknowledges
support from DST-FIST-AIMT and DST-PURSE at Amity University, Rajasthan, India. The graphical
abstract was created with BioRender.com [Created in BioRender. Singh DD (2025)].
Authors’ contributions
Conceptualization, investigation, writing - original draft, review and editing: Singh DD
Conceptualization, investigation, writing - original draft, review and editing: Yadav DK
Supervision, resources, review and editing: Shin D
All authors have read and approved the final manuscript.
Availability of data and materials
Not applicable.
Financial support and sponsorship
This study was funded by the National Research Foundation of Korea (grant numbers: RS-2020-NR049589
and RS-2025-00555975). This work was also supported by the Gachon University Research Fund of 2022
(GCU-202206050001).
Conflicts of interest
All authors declared that there are no conflicts of interest.
Ethical approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Copyright
© The Author(s) 2025.
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