Background and Objectives: Pancreatic and colorectal cancers are frequently diagnosed at advanced stages, significantly limiting treatment options and reducing survival rates. To address this critical challenge, non-invasive early detection methods that leverage circulating tumor DNA (ctDNA) for identifying tumor-specific genetic mutations in plasma have been proposed. ctDNA analysis provides a high-precision, dynamic approach for detecting molecular signatures of cancer at earlier stages compared to traditional diagnostic methods such as endoscopy, imaging, or biopsy, which are often limited to identifying tumors in advanced stages. Methods: This review examines current research on next-generation sequencing (NGS) and highly sensitive digital PCR techniques for detecting minimal amounts of ctDNA shed by cancer cells into the bloodstream. By evaluating the technological advancements and methodologies used for ctDNA analysis, this review explores the potential of these approaches for early detection, continuous monitoring of ctDNA fluctuations, and real-time assessment of tumor progression or therapy response. Results: The reviewed studies demonstrate the capacity of ctDNA analysis for early cancer detection and personalized disease monitoring. Its ability to provide dynamic, molecular-level insights makes it particularly valuable for high-risk populations with genetic predispositions to pancreatic and colorectal cancers. However, challenges remain, including enhancing the sensitivity and specificity of ctDNA detection to accurately differentiate between benign and malignant alterations. Conclusions: ctDNA-based early detection has the potential to revolutionize cancer screening and patient management, offering a personalized and non-invasive approach to identifying and monitoring pancreatic and colorectal cancers. Further research is necessary to optimize detection technologies, validate their effectiveness across diverse populations, and integrate these methods into clinical practice. This innovative strategy holds promise for improving early diagnosis and therapeutic outcomes, ultimately transforming the landscape of cancer care.
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