This study investigates the role of ubiquitin-specific protease 7 (USP7) in gastric cancer (GC) and explores the potential of a novel USP7 inhibitor, DHPO, in treating GC. USP7 is identified as a key player in GC development, immune response, and chemo-resistance. In vitro and in vivo experiments demonstrate that DHPO, a potent USP7 inhibitor, significantly抑制了GC细胞的增殖、迁移和侵袭能力，并抑制了肿瘤生长和转移。DHPO诱导的细胞死亡表现为铁依赖性脂质过氧化、线粒体膜破坏、丙二醛（MDA）积累和铁过载，这与USP7调控的脂肪酸合成酶（SCD）的去泛素化和降解有关。进一步的研究揭示了USP7通过去泛素化SCD来调节铁依赖性细胞死亡的机制。此外，DHPO在患者来源的异种移植（PDX）模型中也显示出抑制肿瘤生长和延长生存期的效果，且没有明显的毒性。这些结果表明，DHPO作为USP7抑制剂，在GC治疗中具有潜在的应用价值。This study investigates the role of ubiquitin-specific protease 7 (USP7) in gastric cancer (GC) and explores the potential of a novel USP7 inhibitor, DHPO, in treating GC. USP7 is identified as a key player in GC development, immune response, and chemo-resistance. In vitro and in vivo experiments demonstrate that DHPO, a potent USP7 inhibitor, significantly抑制了GC细胞的增殖、迁移和侵袭能力，并抑制了肿瘤生长和转移。DHPO诱导的细胞死亡表现为铁依赖性脂质过氧化、线粒体膜破坏、丙二醛（MDA）积累和铁过载，这与USP7调控的脂肪酸合成酶（SCD）的去泛素化和降解有关。进一步的研究揭示了USP7通过去泛素化SCD来调节铁依赖性细胞死亡的机制。此外，DHPO在患者来源的异种移植（PDX）模型中也显示出抑制肿瘤生长和延长生存期的效果，且没有明显的毒性。这些结果表明，DHPO作为USP7抑制剂，在GC治疗中具有潜在的应用价值。