Targeting IAP proteins for therapeutic intervention in cancer

被引：665

作者：

Fulda, Simone ^{[1
]}

Vucic, Domagoj ^{[2
]}

机构：

[1] Goethe Univ Frankfurt, Inst Expt Canc Res Pediat, D-60528 Frankfurt, Germany

[2] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2012年 / 11卷 / 02期

关键词：

NF-KAPPA-B; X-LINKED-INHIBITOR; TRAIL-INDUCED APOPTOSIS; MITOCHONDRIA-DERIVED ACTIVATOR; HUMAN PROSTATE-CANCER; RENAL-CELL CARCINOMA; XIAP ANTISENSE OLIGONUCLEOTIDE; IRRADIATION-INDUCED APOPTOSIS; ACUTE MYELOID-LEUKEMIA; PROGNOSTIC-SIGNIFICANCE;

D O I：

10.1038/nrd3627

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Evasion of apoptosis is one of the crucial acquired capabilities used by cancer cells to fend off anticancer therapies. Inhibitor of apoptosis (IAP) proteins exert a range of biological activities that promote cancer cell survival and proliferation. X chromosome-linked IAP is a direct inhibitor of caspases-pro-apoptotic executioner proteases-whereas cellular IAP proteins block the assembly of pro-apoptotic protein signalling complexes and mediate the expression of anti-apoptotic molecules. Furthermore, mutations, amplifications and chromosomal translocations of IAP genes are associated with various malignancies. Among the therapeutic strategies that have been designed to target IAP proteins, the most widely used approach is based on mimicking the IAP-binding motif of second mitochondria-derived activator of caspase (SMAC), which functions as an endogenous IAP antagonist. Alternative strategies include transcriptional repression and the use of antisense oligonucleotides. This Review provides an update on IAP protein biology as well as current and future perspectives on targeting IAP proteins for therapeutic intervention in human malignancies.

引用

页码：109 / 124

页数：16

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