{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299214/"]},"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=GSE299214"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Orphan drug nitisinone combined with sorafenib synergistically boosts anti-PD-1 efficacy in MSS Colorectal Cancer [RNA-Seq]","description":"We reveal nitisinone, an FDA-approved tyrosine catabolism inhibitor that targets the HPD enzyme, and sorafenib exert synergistic growth inhibition effects in MSS CRC cells, organoids and mouse xenografts. Using co-cultures of PBMCs with autologous tumor organoids, orthotopic transplant models, multiplex immunostaining and scRNA-seq, we verify that the combination of nitisinone and sorafenib synergistically enhances anti-PD-1 efficacy in a manner that is dependent on the mtDNA-cGAS-STING axis and recruits and activates NK cells. Collectively, the “Triplet” therapy (nitisinone+sorafenib+anti-PD-1) not only achieves an excellent therapeutic effect but also has a favorable safety profile, potentially facilitating expanded access indications of nitisinone in future MSS CRC treatment strategies.","dates":{"publication":"2026/06/30"},"accession":"GSE299214","cross_references":{"GSM":["GSM9035226","GSM9035227","GSM9035228","GSM9035229","GSM9035230","GSM9035231"],"GPL":["24676"],"GSE":["299214"],"taxon":["Homo sapiens"]}}