Journal: Nature reviews. Clinical oncology
This review focuses on the current and emerging roles of circulating tumor DNA (ctDNA) analysis from liquid biopsy in the management of colorectal cancer.
Key points:
- Tumor heterogeneity and resistance: Colorectal cancer is molecularly heterogeneous, and evolving pathway alterations contribute to progression and treatment resistance, particularly in the metastatic setting.
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Metastatic disease – real-time molecular profiling:
- • ctDNA from liquid biopsy is used to capture tumor molecular heterogeneity and clonal evolution.
- • It enables identification of actionable genomic alterations for precision oncology (for example, predicting eligibility for targeted therapies).
- • Serial ctDNA assessments can detect emerging resistance mechanisms under treatment pressure, supporting adaptive treatment strategies.
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Localized disease – minimal residual disease (MRD):
- • ctDNA detection after surgery or locoregional therapy has been clinically validated as a marker of MRD in colon and rectal cancer.
- • Post-treatment ctDNA status offers refined prognostic stratification beyond standard clinicopathologic factors.
- • This can inform adjuvant therapy decisions—escalating treatment in ctDNA-positive patients at higher relapse risk and potentially de-escalating in ctDNA-negative patients to reduce overtreatment.
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Technological evolution and comprehensive genomic profiling (CGP):
- • The field has moved from PCR-based assays focused on a few mutations to broad next-generation sequencing panels assessing hundreds of genes.
- • Liquid biopsy-based CGP provides a more complete picture of an individual patient’s tumor genomics and its temporal evolution.
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Clinical implications:
- • Liquid biopsy is minimally invasive and easily repeatable, allowing dynamic monitoring over the disease course.
- • The authors summarize evidence for current clinical applications in metastatic colorectal cancer and review data supporting integration of MRD-directed strategies in earlier-stage disease, with the dual goals of improving cure rates and limiting unnecessary systemic therapy.
Overall, the article positions ctDNA-based liquid biopsy—particularly when coupled with comprehensive genomic profiling—as a central tool for personalized, adaptive management of colorectal cancer across both metastatic and localized settings.