Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
Cells. 2020 Feb 11;9(2):406. doi: 10.3390/cells9020406.
It is well accepted that the ability of cancer cells to circumvent the cell death program that untransformed cells are subject to helps promote tumor growth. Strategies designed to reinstate the cell death program in cancer cells have therefore been investigated for decades. Overexpression of members of the Inhibitor of APoptosis (IAP) protein family is one possible mechanism hindering the death of cancer cells. To promote cell death, drugs that mimic natural IAP antagonists, such as second mitochondria-derived activator of caspases (Smac/DIABLO) were developed. Smac-Mimetics (SMs) have entered clinical trials for hematological and solid cancers, unfortunately with variable and limited results so far. This review explores the use of SMs for the treatment of cancer, their potential to synergize with up-coming treatments and, finally, discusses the challenges and optimism facing this strategy.
人们普遍认为，癌细胞逃避未转化细胞所受的细胞死亡程序的能力有助于促进肿瘤生长。因此，数十年来一直在研究旨在恢复癌细胞中的细胞死亡程序的策略。凋亡抑制蛋白（IAP）家族成员的过表达是一种可能阻碍癌细胞死亡的机制。为了促进细胞死亡，开发了模仿天然 IAP 拮抗剂的药物，例如第二线粒体衍生的半胱天冬酶激活剂（Smac/DIABLO）。Smac 模拟物（SMs）已进入血液系统恶性肿瘤和实体瘤的临床试验，但迄今为止结果各不相同且有限。本文综述了 SMs 治疗癌症的应用、与即将出现的治疗方法协同作用的潜力，并最终讨论了这一策略面临的挑战和乐观前景。
