Dubrez Laurence, Berthelet Jean, Glorian Valérie
Institut National de la Santé et de la Recherche Médicale (Inserm), Dijon, France ; Université de Bourgogne, Dijon, France.
Onco Targets Ther. 2013 Sep 16;9:1285-304. doi: 10.2147/OTT.S33375.
The inhibitors of apoptosis (IAPs) constitute a family of proteins involved in the regulation of various cellular processes, including cell death, immune and inflammatory responses, cell proliferation, cell differentiation, and cell motility. There is accumulating evidence supporting IAP-targeting in tumors: IAPs regulate various cellular processes that contribute to tumor development, such as cell death, cell proliferation, and cell migration; their expression is increased in a number of human tumor samples, and IAP overexpression has been correlated with tumor growth, and poor prognosis or low response to treatment; and IAP expression can be rapidly induced in response to chemotherapy or radiotherapy because of the presence of an internal ribosome entry site (IRES)-dependent mechanism of translation initiation, which could contribute to resistance to antitumor therapy. The development of IAP antagonists is an important challenge and was subject to intense research over the past decade. Six molecules are currently in clinical trials. This review focuses on the role of IAPs in tumors and the development of IAP-targeting molecules for anticancer therapy.
凋亡抑制蛋白（IAPs）构成了一个参与多种细胞过程调节的蛋白质家族，这些过程包括细胞死亡、免疫和炎症反应、细胞增殖、细胞分化以及细胞运动。越来越多的证据支持在肿瘤中靶向IAPs：IAPs调节多种促进肿瘤发展的细胞过程，如细胞死亡、细胞增殖和细胞迁移；它们在许多人类肿瘤样本中的表达增加，并且IAPs过表达与肿瘤生长、预后不良或对治疗反应低相关；由于存在依赖内部核糖体进入位点（IRES）的翻译起始机制，IAPs的表达可在化疗或放疗后迅速诱导，这可能导致对抗肿瘤治疗产生耐药性。IAP拮抗剂的开发是一项重要挑战，并且在过去十年中受到了广泛研究。目前有六种分子正在进行临床试验。本综述重点关注IAPs在肿瘤中的作用以及用于抗癌治疗的IAP靶向分子的开发。
