IAP proteins as targets for drug development in oncology.
IAP proteins as targets for drug development in oncology.
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DOI：
10.2147/ott.s33375
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发表时间：
2013-09-16
影响因子：
4
通讯作者：
Glorian V
中科院分区：
文献类型：
--
作者：
Dubrez L;Berthelet J;Glorian V
细胞凋亡抑制剂（IAP）是一类参与调控细胞死亡、免疫和炎症反应、细胞增殖、细胞分化和细胞运动的蛋白质家族。越来越多的证据支持IAP在肿瘤中的靶向作用：IAP调节各种有助于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品中的表达增加，并且IAP过表达与肿瘤生长、预后差或对治疗的低反应相关;由于存在内部核糖体进入位点（IRES）依赖的翻译起始机制，IAP的表达可以在化疗或放疗后迅速诱导，这可能有助于抗肿瘤治疗。IAP拮抗剂的开发是一个重要的挑战，在过去十年中进行了大量的研究。目前有六种分子正在进行临床试验。本文综述了IAP在肿瘤中的作用以及IAP靶向分子在抗肿瘤治疗中的应用。
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.