Abstract
Comprehensive genomic profiling using next-generation sequencing (NGS) enables the identification of multiple genomic biomarkers established in advanced gastrointestinal (GI) cancers. However, tissue-based NGS has limitations, such as long turnaround time and failure to detect tumour heterogeneity. Recently, the analysis of circulating tumour DNA (ctDNA) using polymerase chain reaction-based or NGS-based methods has demonstrated the capability to detect genomic alterations with high accuracy compared with tumour tissue analysis with short turnaround time and identify heterogeneous resistance mechanisms. Furthermore, ctDNA analysis can be repeatedly performed on disease progression to clarify resistant clones. Clinical trials that test the outcome of a selected targeted therapy based on a ctDNA result are ongoing to prospectively evaluate the clinical utility of ctDNA analysis. Furthermore, the improvement of ctDNA analysis beyond current technical limits of mutation-based ctDNA detection methods has expanded the potential for detecting the presence of tumours in patients with no clinically evident disease, such as minimal residual disease and early cancer. Although a careful understanding of the advantages and limitations are required and further prospective studies are needed, the ctDNA analysis has the potential to overcome several challenges in the treatment of various types of cancers at all stages, including GI cancers.