Abstract
BACKGROUND: Liquid biopsy with circulating tumor DNA (ctDNA) has rapidly emerged as a new paradigm for assessing tumor burden, genetic heterogeneity, and therapeutic response in a real-time, noninvasive manner. However, ctDNA is often visually low (sometimes < 0.1% of the total circulating cell-free DNA), creating a significant challenge for reliable detection (especially for early-stage disease and minimal residual disease). DISCUSSION: New technologies for structural variant (SV)-based ctDNA assays, nanomaterial-based electrochemical sensors, magnetic nano-electrode platforms, and fragment-enriched library preparation have improved sensitivity to attomolar concentrations and less in some populations. In some cancers, ctDNA may provide early evidence of recurrence (i.e., > 1 year) before being clinically evident using traditional metrics. These technologies allow for unprecedented opportunities and sensitivity for early detection, monitoring of treatment response, and early detection of molecular recurrence. Nevertheless, a barrier remains for widespread clinical application owing to pre-analytical technique variability, analytical platform variability, cost, and the necessity of large-scale, prospective trials. CONCLUSION: This study will analyze new innovative technology-based ultrasensitive ctDNA assay detection and future research and clinical applications for breast, colorectal, lung, lymphoid, and gastroesophageal cancers, and studies assessing ctDNA for monitoring treatment. Prospects for ctDNA detection utilizing multiplexed CRISPR-Cas ctDNA assays, microfluidic point-of-care (POC) devices, and AI-based error suppression methods may be the next horizon for ctDNA liquid biopsy technology.