Circulating Tumor DNA Sequencing: Clinical Applications, Technological Advancements, and Future Prospects in Cancer Management

Abstract Background: Cell-free DNA (cfDNA) analysis through liquid biopsy has emerged as a transformative tool in cancer management, offering minimally invasive alternatives to traditional tissue biopsies. This has significant practical implications, particularly considering that metastasis accounts for approximately 90% of cancer deaths. Methods: This comprehensive review synthesizes technological advances in cfDNA sequencing with real-world clinical applications. We examined cfDNA sequencing platforms, including next-generation sequencing, digital PCR, and methylation-based approaches across various oncological applications. A detailed case study of TP53 L257Q mutation in squamous cell carcinoma demonstrates clinical implementation using a 206-gene panel with detection sensitivity below 0.5% variant allele frequency. Results: ctDNA analysis enables the detection of key mutations in genes such as TP53 and EGFR, guiding treatment decisions when tissue biopsies are inaccessible. The technology facilitates real-time monitoring of treatment response, detection of resistance mechanisms, and identification of minimal residual disease. Integrating artificial intelligence and multi-analyte approaches enhances diagnostic accuracy and enables personalized cancer management strategies. Conclusion: cfDNA-based liquid biopsy revolutionizes cancer diagnostics by providing timely, repeatable genomic surveillance. While challenges remain in early-stage detection and standardization protocols, integrating ctDNA analysis with other biomarkers and clinical data holds significant promise for optimizing cancer management and improving patient outcomes.