Liu Jiao, Dai Enyong, Kang Rui, Kroemer Guido, Tang Daolin
Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
Oncoimmunology. 2021 Jan 4;10(1):1868691. doi: 10.1080/2162402X.2020.1868691.
Drug-induced ferroptosis, an iron-dependent regulatory necrosis, has been proposed for the therapy of pancreatic ductal adenocarcinoma. However, genetically engineered mouse models have revealed that high-iron diets or deletion of pancreatic GPX4 (a key repressor of ferroptosis) accelerate the development of mutant -driven PDAC by activating the STING1/TMEM173-dependent DNA sensor pathway. ADM: acinar-to-ductal metaplasia; CGAS: cyclic GMP-AMP synthase; DAMP: damage-associated molecular pattern; GPX4: glutathione peroxidase 4; GEMM: genetically engineered mouse models; PDAC: pancreatic ductal adenocarcinoma; PanIN: pancreatic intraepithelial neoplasia, SLC7A11: solute carrier family 7 member 11; STING1: cGAMP-stimulator of interferon response cGAMP interactor 1; TME: tumor microenvironment; 8-OHG: 8-hydroxy-2'-deoxyguanosine.
药物诱导的铁死亡是一种铁依赖性调节性坏死，已被提出用于治疗胰腺导管腺癌。然而，基因工程小鼠模型显示，高铁饮食或胰腺GPX4（铁死亡的关键抑制因子）的缺失通过激活STING1/TMEM173依赖性DNA传感途径加速了突变驱动的胰腺导管腺癌的发展。ADM：腺泡-导管化生；CGAS：环状GMP-AMP合酶；DAMP：损伤相关分子模式；GPX4：谷胱甘肽过氧化物酶4；GEMM：基因工程小鼠模型；胰腺导管腺癌；PanIN：胰腺上皮内瘤变，SLC7A11：溶质载体家族7成员11；STING1：干扰素反应cGAMP相互作用因子1的cGAMP刺激物；TME：肿瘤微环境；8-OHG：8-羟基-2'-脱氧鸟苷。
