Liquid biopsies represent a transformative shift in cancer diagnostics, moving beyond traditional imaging to detect minimal residual disease through circulating tumor DNA (ctDNA). Unlike protein-based biomarkers, which often suffer from poor specificity, ctDNA analysis tracks specific cancer-associated mutations, providing a highly precise marker for disease recurrence. While current clinical applications focus on genotyping metastatic disease, the field is advancing toward early detection and guiding adjuvant therapy by identifying microscopic tumor burdens before they manifest on CT or MRI scans. Challenges remain in achieving the sensitivity required for early-stage screening, where ctDNA levels are extremely low, and in distinguishing cancer-derived signals from age-related clonal hematopoiesis. Integrating mutation analysis with methylation patterns and fragmentomics offers a promising path toward high-confidence, non-invasive screening that could significantly improve cancer survival rates by enabling earlier, more targeted interventions.
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