Dual Biomarker Strategies for Liquid Biopsy: Integrating Circulating Tumor Cells and Circulating Tumor DNA for Enhanced Tumor Monitoring.

The liquid biopsy has gained significant attention in cancer diagnostics, with circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) being recognized as key biomarkers for tumor detection and monitoring. However, each biomarker possesses inherent limitations that restrict its standalone clinical utility, such as the rarity and heterogeneity of CTCs and the variable sensitivity and specificity of ctDNA assays. This highlights the necessity of integrating both biomarkers to maximize diagnostic and prognostic potential, offering a more comprehensive understanding of the tumor biology and therapeutic response. In this review, we summarize clinical studies that have explored the combined analysis of CTCs and ctDNA as biomarkers, providing insights into their synergistic value in diverse tumor types. Specifically, this paper examines the individual advantages and limitations of CTCs and ctDNA, details the findings of combined biomarker studies across various cancers, highlights the benefits of dual biomarker approaches over single-biomarker strategies, and discusses future prospects for advancing personalized oncology through liquid biopsies. By offering a comprehensive overview of clinical studies combining CTCs and ctDNA, this review serves as a guideline for researchers and clinicians aiming to enhance biomarker-based strategies in oncology and informs biosensor design for improved biomarker detection.