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Review
. 2025 Jul 30;17(15):2520.
doi: 10.3390/cancers17152520.

Integrating Circulating Tumor DNA into Clinical Management of Colorectal Cancer: Practical Implications and Therapeutic Challenges

Nikhil Vojjala  1 , Viktoriya Gibatova  2 , Raj N Shah  3 , Sakshi Singal  4 , Rishab Prabhu  1 , Geetha Krishnamoorthy  1 , Karen Riggins  5 , Nagaishwarya Moka  6
Affiliations
Review

Integrating Circulating Tumor DNA into Clinical Management of Colorectal Cancer: Practical Implications and Therapeutic Challenges

Nikhil Vojjala et al. Cancers (Basel). .

Abstract

The American Cancer Society estimates that over 152,000 new cases of colorectal cancer (CRC) were diagnosed in 2024, with more than 105,000 cases affecting the colon and 46,000 involving the rectum. CRC remains the second leading cause of cancer-related deaths in the United States, with an estimated 53,010 deaths in 2024. In the era of precision medicine, which incorporates molecular and environmental information into clinical decision-making, identifying patients harboring a deficiency in Deoxyribonucleic acid (DNA) repair allowed for targeted immunotherapies and significantly reduced CRC-related mortality. A significant advancement in this domain is the application of liquid biopsy, which has emerged as a promising tool for prognostication, guiding therapy, and monitoring treatment response in CRC. This review aims to comprehensively explore the role of liquid biopsy in colorectal malignancies, describing its practical applications, prognostic significance, and potential to revolutionize CRC management in the future. At the end, we also aim to show a schematic representation of showing integration of Circulating Tumor (Ct) DNA in routine clinical management of CRC. The highlight of this article is the structured and evidence-based schematic framework and its integration into future practice. The schematic pathway is designed to optimize ctDNA utilization across various stages of colorectal cancer management.

Keywords: colorectal cancer; ctDNA; prognosis; surveillance.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Detection and analysis of ctDNA for application in colorectal cancer management. This figure shows a schematic representation of various methods available for ctDNA detection, which will further guide in diagnosis, prognosis, therapy guidance, and surveillance. ctDNA: Circulating tumor Deoxyribonucleic acids, qPCR: Quantitative polymerase chain reaction, ddPCR: Digital droplet PCR, NGS: Next Generation Sequencing.
Figure 2
Figure 2
Current challenges of ctDNA analysis and proposed practical solutions. This is a flowchart depicting the challenges of the applications of ctDNA and practical solutions.
Figure 3
Figure 3
This figure demonstrates the current application of the ctDNA in the management of colorectal cancer, starting from early diagnosis to monitoring treatment response.
Figure 4
Figure 4
A schematic diagram shows ctDNA application in the management of colorectal cancer. The top green colored flow represents current standards of screening, diagnosis and follow-up. The bottom flow chart represents the futuristic applications of ctDNA at various stages in the management of CRC.
See this image and copyright information in PMC

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