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Volume 26
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Review

Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions

by
Pina Ziranu
1,*,
Andrea Pretta
1,
Giorgio Saba
1,
Dario Spanu
1,
Clelia Donisi
1,
Paolo Albino Ferrari
2,
Flaviana Cau
3,
Alessandra Pia D’Agata
1,
Monica Piras
3,
Stefano Mariani
1,
Marco Puzzoni
1,
Valeria Pusceddu
1,
Ferdinando Coghe
4,
Gavino Faa
3,5 and
Mario Scartozzi
1
1
Medical Oncology Unit, University Hospital and University of Cagliari, 09042 Cagliari, Italy
2
Division of Thoracic Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione “G. Brotzu”, 09121 Cagliari, Italy
3
Department of Medical Sciences and Public Health, University of Cagliari, 09042 Cagliari, Italy
4
Clinical-Microbiological Laboratory, University Hospital of Cagliari, 09042 Cagliari, Italy
5
Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(15), 7619; https://doi.org/10.3390/ijms26157619
Submission received: 29 May 2025 / Revised: 25 July 2025 / Accepted: 27 July 2025 / Published: 6 August 2025
(This article belongs to the Special Issue Cancer Biology and Epigenetic Modifications)
Review Reports Versions Notes

Abstract

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages.
Keywords: liquid biopsy; colorectal cancer; minimal residual disease; resistance mechanisms; adjuvant therapy guidance liquid biopsy; colorectal cancer; minimal residual disease; resistance mechanisms; adjuvant therapy guidance

Share and Cite

MDPI and ACS Style

Ziranu, P.; Pretta, A.; Saba, G.; Spanu, D.; Donisi, C.; Ferrari, P.A.; Cau, F.; D’Agata, A.P.; Piras, M.; Mariani, S.; et al. Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions. Int. J. Mol. Sci. 2025, 26, 7619. https://doi.org/10.3390/ijms26157619

AMA Style

Ziranu P, Pretta A, Saba G, Spanu D, Donisi C, Ferrari PA, Cau F, D’Agata AP, Piras M, Mariani S, et al. Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions. International Journal of Molecular Sciences. 2025; 26(15):7619. https://doi.org/10.3390/ijms26157619

Chicago/Turabian Style

Ziranu, Pina, Andrea Pretta, Giorgio Saba, Dario Spanu, Clelia Donisi, Paolo Albino Ferrari, Flaviana Cau, Alessandra Pia D’Agata, Monica Piras, Stefano Mariani, and et al. 2025. "Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions" International Journal of Molecular Sciences 26, no. 15: 7619. https://doi.org/10.3390/ijms26157619

APA Style

Ziranu, P., Pretta, A., Saba, G., Spanu, D., Donisi, C., Ferrari, P. A., Cau, F., D’Agata, A. P., Piras, M., Mariani, S., Puzzoni, M., Pusceddu, V., Coghe, F., Faa, G., & Scartozzi, M. (2025). Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions. International Journal of Molecular Sciences, 26(15), 7619. https://doi.org/10.3390/ijms26157619

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