Apoptosis and cancer: mutations within caspase genes

被引：566

作者：

Ghavami, S. ^{[2
,3
,4
]}

Hashemi, M. ^{[5
,6
]}

Ande, S. R. ^{[7
]}

Yeganeh, B. ^{[8
,9
]}

Xiao, W. ^{[7
]}

Eshraghi, M. ^{[7
,8
,9
]}

Bus, C. J. ^{[1
]}

Kadkhoda, K. ^{[10
]}

Wiechec, E. ^{[11
]}

Halayko, A. J. ^{[2
,3
,4
]}

Los, M. ^{[1
]}

机构：

[1] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany

[2] Univ Manitoba, Dept Physiol, Winnipeg, MB, Canada

[3] Univ Manitoba, Natl Training Program Allergy & Asthma, Winnipeg, MB, Canada

[4] Manitoba Inst Child Hlth, Biol Breathing Grp, Winnipeg, MB, Canada

[5] Zahedan Univ Med Sci, Dept Clin Biochem, Zahedan, Iran

[6] Zahedan Univ Med Sci, Cellular Mol Res Ctr, Zahedan, Iran

[7] CancerCare Manitoba, MICB, Winnipeg, MB, Canada

[8] Univ Manitoba, Fac Med, Inst Cardiovasc Sci, St Boniface Gen Hosp,Res Ctr, Winnipeg, MB, Canada

[9] Univ Manitoba, Fac Med, Inst Cardiovasc Sci, St Boniface Gen Hosp,Dept Biochem & Med Genet, Winnipeg, MB, Canada

[10] Diagnost Serv Manitoba, Winnipeg, MB, Canada

[11] Univ Aarhus, Dept Human Genet, Aarhus, Denmark

来源：

JOURNAL OF MEDICAL GENETICS | 2009年 / 46卷 / 08期

关键词：

ENDOPLASMIC-RETICULUM STRESS; TRAIL-INDUCED APOPTOSIS; DRUG-INDUCED APOPTOSIS; INDUCED CELL-DEATH; RIBOZYME-MEDIATED INHIBITION; X-LINKED INHIBITOR; BREAST-CANCER; PANCREATIC-CANCER; CYTOCHROME-C; LUNG-CANCER;

D O I：

10.1136/jmg.2009.066944

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The inactivation of programmed cell death has profound effects not only on the development but also on the overall integrity of multicellular organisms. Beside developmental abnormalities, it may lead to tumorigenesis, autoimmunity, and other serious health problems. Deregulated apoptosis may also be the leading cause of cancer therapy chemoresistance. Caspase family of cysteinyl-proteases plays the key role in the initiation and execution of programmed cell death. This review gives an overview of the role of caspases, their natural modulators like IAPs, FLIPs, and Smac/Diablo in apoptosis and upon inactivation, and also in cancer development. Besides describing the basic mechanisms governing programmed cell death, a large part of this review is dedicated to previous studies that were focused on screening tumours for mutations within caspase genes as well as their regulators. The last part of this review discusses several emerging treatments that involve modulation of caspases and their regulators. Thus, we also highlight caspase cascade modulating experimental anticancer drugs like cFLIP-antagonist CDDO-Me; cIAP1 antagonists OSU-03012 and ME-BS; and XIAP small molecule antagonists 1396-11, 1396-12, 1396-28, triptolide, AEG35156, survivin/Hsp90 antagonist shephedrin, and some of the direct activators of procaspase-3.

引用

页码：497 / 510

页数：14

共 206 条

[1] Analyses of apoptotic regulators CASP9 and DFFA at 1p36.2, reveal rare allele variants in human neuroblastoma tumours [J].