SY11-6 - Nationwide cancer genome screening project utilizing circulating tumor DNA analysis for advanced gastrointestinal cancer

Abstract

Liquid biopsy has emerged as an excellent molecular diagnostic tool for assessing spatial and temporal intratumoral heterogeneity in cancer with minimal invasiveness. In colorectal cancer, circulating tumor DNA (ctDNA) analysis can identify not only genomic alterations associated with resistance to anti-EGFR therapy, but also predictive biomarkers to immune checkpoint inhibitors, such as mutations in mismatch repair genes, microsatellite-high phenotype, and tumor mutation burden. Furthermore, the emergence of alterations in genes, such as RAS, EGFR, HER2, and MET, can be detected as acquired resistance mechanisms in specific genes by longitudinally monitoring ctDNAs during treatment. To determine the value of ctDNA analysis for decision-making by more accurate molecular marker-based selection of patients, clinical trials must be refined to evaluate the efficacy of study treatment in patients with targetable genomic alterations confirmed by ctDNA analysis. In addition, resistance biomarkers should be explored by monitoring ctDNA in large-scale clinical trials for identification of resistance mechanisms to targeted therapies. We launched a ctDNA analysis-based cancer genome screening project as part of the SCRUN-Japan GI-SCREEN since February 2018. In our study, genomic alterations in 73 genes in ctDNA from blood have been analyzed using a next-generation sequencing based method for 200 patients with metastatic colorectal cancer. Furthermore, umbrella trials have concurrently been conducted for patients with specific genomic alterations, such as HER2 amplification. Serial monitoring of ctDNA is also planned to explore the resistance biomarkers in each clinical trial. Our project can help to realize cancer precision medicine utilizing ctDNA analysis for metastatic colorectal cancer. In the near future, this project will expand to appropriately 2,000 patients with all advanced gastrointestinal cancers. Updated results will be presented.