Chua MWE, Chan DKH. Challenges and proposed solutions to the adoption of cell free DNA in screening, detecting and prognosticating colorectal cancer. World J Gastrointest Oncol 2025; 17(8): 106663 [DOI: 10.4251/wjgo.v17.i8.106663]
Corresponding Author of This Article
Dedrick Kok-Hong Chan, Assistant Professor, Department of Colorectal Surgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. surckhd@nus.edu.sg
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Aug 15, 2025; 17(8): 106663 Published online Aug 15, 2025. doi: 10.4251/wjgo.v17.i8.106663
Challenges and proposed solutions to the adoption of cell free DNA in screening, detecting and prognosticating colorectal cancer
Megan Wern-Ee Chua, Dedrick Kok-Hong Chan
Megan Wern-Ee Chua, Dedrick Kok-Hong Chan, Department of Colorectal Surgery, National University Hospital, Singapore 119074, Singapore
Author contributions: Chua MWE was responsible for performing a literature review, writing the initial draft of the review, and designing the figure; Chan DKH was responsible for writing the review; Chua MWE and Chan DKH selected eligible studies and final approval of the review; and all authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dedrick Kok-Hong Chan, Assistant Professor, Department of Colorectal Surgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. surckhd@nus.edu.sg
Received: March 4, 2025 Revised: April 8, 2025 Accepted: July 4, 2025 Published online: August 15, 2025 Processing time: 163 Days and 14.3 Hours
Abstract
Detection and treatment of colorectal cancer (CRC) at an early stage is vital for long-term survival. Liquid biopsy has emerged as a promising new avenue for non-invasive screening of CRC as well as prognostication and surveillance of minimal residual disease. Cell free DNA (cfDNA) is a promising liquid biopsy analyte and has been approved for use in clinical practice. Here, we explore the current challenges of utilizing cfDNA in the screening and prognostication of CRC but also for detecting driver mutations in healthy, presymptomatic patients with normal colonic crypts. CfDNA for the detection of cancerous or premalignant colonic lesions has already been extensively explored, however few have considered utilizing cfDNA in the detection of driver mutations in healthy patients. Theoretically, this would allow us to detect patients who are at a higher risk of tumorigenesis decades in advance of established malignancy and stratify them into higher risk groups for early-intervention screening programs. We also explore the solutions necessary to overcome the challenges that prevent liquid biopsy from entering mainstream clinical use. The potential for liquid biopsy is immense if these challenges are successfully circumvented, and can dramatically reduce CRC rates as well as improve survival in patients.
Core Tip: Cell free DNA (cfDNA) carries information about colorectal cancer-specific genetic and epigenetic alterations which can aid in screening, detection and prognostication. Detection of genetic alterations is made difficult by low signal-to-noise ratio owing to an abundance of background non-tumorigenic mutations. Low amounts of cfDNA in healthy individuals negatively affects the sequencing performance and limit of detection of assays making screening non-feasible. One solution is to harvest cfDNA from peritoneal fluid or stool as this is more representative of the primary tumour compared to plasma-derived cfDNA. Alternatively, increasing the sensitivity of sequencing technologies would allow for the detection of low frequency mutations.
