Precision medicine for gastrointestinal cancers

Abstract

We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced gastrointestinal (GI) cancer, called as the SCRUM-Japan GI-SCREEN. This is a collaboration between 24 core cancer centers and 17 pharmaceutical companies. More than 5000 patients have been screened and seventy-one patients have been enrolled for clinical trials base on targetable genomic alteration. Examples of ongoing or planning clinical trials include targeting therapies for HER2, BRAFV600E, BRAF non-V600, MET and high tumor mutations burdens. Circulating Tumor DNA analysis is also incorporated as an additional project, which may potentially overcome intra tumor heterogeneity or clonal evolution. An exploratory immune monitoring study is also ongoing to elucidate resistance mechanism of immune check point inhibitors. Tumor samples and PBMC samples are collected and analyzed for immune phenotype using FCM, cyTOF, single cell RNA sequences as well as mutational status and microbiomes, which preliminary show potential correlation between several immune parameters and clinical outcomes. Also, several investigator initiated trials are ongoing to evaluate combination strategies. We hope these attempts may become breakthrough to improve the outcome of patients with advanced GI cancers.