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Exploring Innovations in Colorectal Cancer Screening: Liquid Biopsy and Beyond

NextEdge Admin

19 May 2024

3 min 15 sec

Colorectal cancer (CRC) remains a significant global health challenge due to its high incidence and mortality rates. Despite advancements in treatment, identifying patients who could benefit from specific therapies remains challenging. Traditional tissue biopsies have limitations such as spatial and temporal heterogeneity. Liquid biopsy (LB), particularly circulating tumor DNA (ctDNA) analysis, emerges as a promising alternative, offering insights into CRC’s molecular complexity with minimal invasiveness.

CtDNA monitoring enables real-time assessment of genomic changes in both non-metastatic and metastatic CRC. Current detection assays, including PCR-based technologies and next-generation sequencing (NGS), offer increased sensitivity and specificity, expanding the scope of genetic alterations detected. Whole-genome sequencing (WGS) provides comprehensive genomic analysis, albeit with higher costs.

However, ctDNA analysis faces technical challenges like achieving low limits of detection and detecting a broad spectrum of genetic alterations. Ongoing research aims to validate its clinical utility further, with prospective trials evaluating its role in guiding treatment decisions.

Utilizing cell-free DNA (cfDNA) for CRC screening has been explored since the discovery of ctDNA. While CRC patients have elevated levels of mutated DNA, widespread clinical use is hindered by suboptimal limits of detection, especially for small invasive cancers or precancerous lesions.

Strategies to address this include verifying panels of frequently mutated genes in CRC and integrating cancer protein biomarkers with mutational panels. Other approaches focus on cancer genome features as biomarkers, such as studying methylation patterns and DNA fragment length analysis.

Analysis of cfDNA derived from stool has also been proposed to enhance the sensitivity of non-invasive fecal tests like FIT. Multitarget stool DNA testing shows improved sensitivity for CRC and detection of high-grade dysplasia polyps, albeit with higher false-positive rates.

While cfDNA analysis holds promise for CRC screening, its widespread adoption in clinical practice awaits further validation and refinement. It may complement existing screening tools rather than replace them entirely. Other screening methods, including colonoscopy, fecal occult blood testing, and flexible sigmoidoscopy, remain crucial in CRC detection and prevention efforts.