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Orphan drug nitisinone combined with sorafenib synergistically boosts anti-PD-1 efficacy in MSS Colorectal Cancer [RNA-Seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE299214 | GEO | 2026/06/30

REPOSITORIES: GEO

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Orphan drug nitisinone combined with sorafenib synergistically boosts anti-PD-1 efficacy in MSS Colorectal Cancer [RNA-Seq]

Project description:Orphan drug nitisinone combined with sorafenib synergistically boosts anti-PD-1 efficacy in MSS Colorectal Cancer [RNA-Seq]

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