Fulda Simone
Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstr. 3a, 60528 Frankfurt, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Semin Cell Dev Biol. 2015 Mar;39:132-8. doi: 10.1016/j.semcdb.2014.12.005. Epub 2014 Dec 27.
As the Inhibitor of Apoptosis (IAP) proteins are expressed at high levels in human cancers, they represent promising targets for therapeutic intervention. Small-molecule inhibitors of IAP proteins mimicking the endogenous IAP antagonist Smac, called Smac mimetics, neutralize IAP proteins and thereby promote the induction of cell death. Smac mimetics have been shown in preclinical models of human cancer to directly trigger cancer cell death or to sensitize for cancer cell death induced by a variety of cytotoxic stimuli. Smac mimetics are currently undergoing clinical evaluation in phase I/II trials, demonstrating that therapeutic targeting of IAP proteins has reached the clinical stage.
由于凋亡抑制蛋白（IAP）在人类癌症中高表达，它们是治疗干预的有前景的靶点。模拟内源性IAP拮抗剂Smac的IAP蛋白小分子抑制剂，即Smac模拟物，可中和IAP蛋白，从而促进细胞死亡的诱导。在人类癌症的临床前模型中已表明，Smac模拟物可直接触发癌细胞死亡或使癌细胞对多种细胞毒性刺激诱导的细胞死亡敏感。Smac模拟物目前正在进行I/II期临床试验评估，这表明对IAP蛋白的治疗靶向已进入临床阶段。
