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凋亡抑制剂:癌症中的临床意义。

Inhibitors of apoptosis: clinical implications in cancer.

机构信息

Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Kingdom of Saudi Arabia.

Department of Chemistry, Biochemistry Speciality, Faculty of Science, Cairo University, Giza, Egypt.

出版信息

Apoptosis. 2017 Dec;22(12):1487-1509. doi: 10.1007/s10495-017-1429-4.

Abstract

Inhibitor of apoptosis (IAP) family comprises a group of endogenous proteins that function as main regulators of caspase activity and cell death. They are considered the main culprits in evasion of apoptosis, which is a fundamental hallmark of carcinogenesis. Overexpression of IAP proteins has been documented in various solid and hematological malignancies, rendering them resistant to standard chemotherapeutics and radiation therapy and conferring poor prognosis. This observation has urged their exploitation as therapeutic targets in cancer with promising pre-clinical outcomes. This review describes the structural and functional features of IAP proteins to elucidate the mechanism of their anti-apoptotic activity. We also provide an update on patterns of IAP expression in different tumors, their impact on treatment response and prognosis, as well as the emerging investigational drugs targeting them. This aims at shedding the light on the advances in IAP targeting achieved to date, and encourage further development of clinically applicable therapeutic approaches.

摘要

凋亡抑制因子 (IAP) 家族是一组内源性蛋白,它们作为半胱氨酸天冬氨酸蛋白酶 (caspase) 活性和细胞死亡的主要调节剂。它们被认为是逃避细胞凋亡的主要元凶,而细胞凋亡是癌症发生的基本特征。已在各种实体瘤和血液恶性肿瘤中记录到 IAP 蛋白的过表达,使它们对标准化疗和放疗产生耐药性,并导致预后不良。这一观察结果促使人们将其作为癌症的治疗靶点进行探索,具有有前景的临床前结果。本综述描述了 IAP 蛋白的结构和功能特征,以阐明其抗凋亡活性的机制。我们还提供了不同肿瘤中 IAP 表达模式的最新信息,以及它们对治疗反应和预后的影响,以及针对它们的新兴研究性药物。这旨在阐明迄今为止在 IAP 靶向方面取得的进展,并鼓励进一步开发临床适用的治疗方法。

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