{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316970/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316970"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CYD-4-61 Suppresses Gastric Tumor Growth by Targeting SOX9–CDK4–Driven Oncogenic Programs and Enhances Anti-PD-1 Therapy","description":"Gastric adenocarcinoma (GAC), particularly with peritoneal carcinomatosis, remains highly lethal and therapeutically refractory. We investigated the anti-tumor activity and mechanisms of CYD-4-61, a small-molecule BAX activator, with emphasis on the SOX9–CDK4 oncogenic axis and tumor immune microenvironment. CYD-4-61 efficacy was evaluated using in vitro GAC models and in vivo xenograft, genetically engineered, and syngeneic mouse models. Bulk, single-cell, and spatial transcriptomics, along with molecular and functional assays, were used to define apoptotic, cell-cycle, and immune-related mechanisms. CYD-4-61 induced BAX-dependent apoptosis and suppressed proliferation, stem-like properties, and tumor growth across multiple GAC models. Transcriptomic analyses revealed inhibition of SOX9-dependent programs, including CDK4, and activation of apoptotic and inflammatory pathways. CYD-4-61 destabilized SOX9 via caspase-dependent cleavage, inhibited cell-cycle progression, activated STING signaling, and enhanced response to PD-1 blockade in immunocompetent models. CYD-4-61 exerts potent anti-tumor effects in GAC by targeting SOX9–CDK4–driven oncogenic programs and modulating immune signaling, supporting its development as a therapeutic agent alone or in combination with immunotherapy.","dates":{"publication":"2026/05/01"},"accession":"GSE316970","cross_references":{"GSM":["GSM9463243","GSM9463232","GSM9463244","GSM9463233","GSM9463234","GSM9463245","GSM9463246","GSM9463235","GSM9463236","GSM9463237","GSM9463238","GSM9463239","GSM9463240","GSM9463241","GSM9463230","GSM9463231","GSM9463242","GSM9463229"],"GPL":["16791"],"GSE":["316970"],"taxon":["Homo sapiens"]}}