The Role of ctDNA in Gastric Cancer

Abstract

Circulating tumour DNA (ctDNA) has potential applications in gastric cancer (GC) with respect to screening, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision making and therapeutic monitoring. It can provide a less invasive and convenient method to capture the tumoural genomic landscape compared to tissue-based next-generation DNA sequencing (NGS). In addition, ctDNA can potentially overcome the challenges of tumour heterogeneity seen with tissue-based NGS. Although the evidence for ctDNA in GC is evolving, its potential utility is far reaching and may shape the management of this disease in the future. This article will review the current and future applications of ctDNA in GC.

Liquid biopsy for gastric cancer: Techniques, applications, and future directions

“…GC detection: For the detection of GC, quantitative analysis of ctDNA (total copy number analysis in blood or serum) or qualitative detection, involving the identification of tumor-specific genetic changes, can be utilized (Table 2 )[ 161 ]. Similar to CTCs, the cfDNA/ctDNA load is found to be higher in GC patients compared to healthy controls or those with preneoplastic lesions, escalating with tumor stage[ 162 ].…”

“…For instance, the analysis of DNA methylation patterns for GC screening, such as the Galleri multicancer detection test, has been explored[ 168 ]. However, the sensitivity of this technique is notably influenced by the disease stage, ranging from 16.7% in stage I GC to 100% in stage IV tumors[ 162 ].…”

Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy

“…Currently, many ongoing clinical trials also are studying the application of ctDNA in cancer prognosis and treatment monitoring regarding colorectal cancer, such as TRACC (NCT04050345) and ADNCirc (NCT02813928), IMPROVE-IT2 (NCT04084249), NCI–sponsored randomized phase II/III COBRA study (NCT0406810), CIRCULATE trial (NCT04120701) and the DYNAMIC-II study (ACTRN12615000381583), the phase II/III DYNAMIC-III study (ACTRN12617001566325), and the phase II/III PROSPECT trial (NCT01515787) and in the OPRA trial (NCT02008656), CHRONOS (NCT03227926) and FIRE-4 (NCT02934529) ( 178 ). And Gastric Cancer clinical trials (NCT04947995、NCT04665687、NCT04511559、NCT05027347、NCT05029869、NCT04943406、NCT04510285、NCT03957564、NCT04817826、NCT04520295、NCT04576858) ( 179 ) and so on.…”

Actionable mutational profiling in solid tumors using hybrid‐capture‐based next‐generation sequencing in a real‐world setting in Spain

“…Next‐generation sequencing (NGS) is a high complex molecular technique that makes it possible to simultaneously test for a very large panel of genes by allowing parallel sequencing of numerous small nucleic acid fragments 3,4 . Compared with other sequencing modalities, NGS holds many advantages, for instance, high throughput to fully sequence all types of mutations for many genes (hundreds to thousands), the sensitivity and the speed 1,2,5 .…”

“…2 Next-generation sequencing (NGS) is a high complex molecular technique that makes it possible to simultaneously test for a very large panel of genes by allowing parallel sequencing of numerous small nucleic acid fragments. 3,4 Compared with other sequencing modalities, NGS holds many advantages, for instance, high throughput to fully sequence all types of mutations for many genes (hundreds to thousands), the sensitivity and the speed. 1,2,5 Moreover, testing in a single assay is both timely and costeffective as it can detect all four main classes of genomic alterations: base substitutions insert and deletions, copy number alterations, and rearrangements or fusions.…”