The clinical utility of circulating tumor DNA in colorectal cancer: A narrative review

ABSTRACT Circulating free DNA (cfDNA) refers to extracellular DNA fragments (50-200 base pairs) in the blood, released during cell apoptosis or necrosis, and linked to tissue injury. Microbial cfDNA (cfmDNA), derived from bacteria, can also be present in both healthy individuals and in patients with colorectal cancer, with some species specific to these categories. Circulating tumor DNA (ctDNA), a subset of cfDNA, originates from tumors and reflects their genetic profile. Elevated ctDNA levels result from increased cell death and impaired clearance during tumor progression. Healthy individuals typically have 30 ng/mL of cfDNA in their blood, whereas patients with cancer can show levels up to 1000 ng/mL. Patients with colon cancer often exhibit higher cfDNA concentrations (500 ng/mL) compared to the patients with rectal cancer (250 ng/mL). ctDNA is a valuable noninvasive biomarker for monitoring colorectal cancer progression and prognosis, particularly since the disease is often diagnosed at advanced stages. Its widespread dispersion of circulating tumor fragments also aids in tracking disease progression and recurrence. This article reviews the life cycle, analysis methods, screening approaches, clinical applications, limitations, and future perspectives of ctDNA. The data for this review were extracted from PubMed, ScienceDirect, ResearchGate, Scopus, and UpToDate, covering publications from January 2016 to December 2023. Out of 95 retrieved articles, 3 were removed before screening. Two were duplicates, and 1 was ineligible record. After reviewing 92 articles for eligibility, 7 were excluded: 3 for being non-human studies, 2 not exclusive to colorectal cancer, and 2 for lacking clinical utility. We selected 85 articles for final analysis. For the purpose of discussion, we have referred to various papers on circulating tumor DNA in colorectal cancer as well ( n = 15).