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Targeting Inhibitors of Apoptosis Proteins (IAPs) For New Breast Cancer Therapeutics

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Abstract

Apoptosis resistance is a hallmark of human cancer. Research in the last two decades has identified key regulators of apoptosis, including inhibitor of apoptosis proteins (IAPs). These critical apoptosis regulators have been targeted for the development of new cancer therapeutics. In this article, we will discuss three members of IAP proteins, namely XIAP, cIAP1 and cIAP2, as cancer therapeutic targets and the progress made in developing new cancer therapeutic agents to target these IAP proteins.

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Abbreviations

AIF:

Apoptosis-Inducing Factor

Apaf-1:

Apoptotic protease activating factor 1

Apo2L:

Apo2 ligand

Apo3L:

Apo3 ligand

Bcl-2:

B-cell lymphoma 2

BIR:

Baculoviral IAP Repeat domain

CARD:

Caspase Recruitment Domain

CD95:

Cluster of Differentiation 95

cFLIP:

cellular FLICE-inhibitory protein

cIAP1:

cellular Inhibitor of Apoptosis Protein 1

cIAP2:

cellular Inhibitor of Apoptosis Proteins 2

dATP:

Deoxyadenosine triphosphate

DIABLO:

Direct IAP-Binding protein with Low PI

DISC:

Death-Inducing Signaling Complex

DR:

Death Receptor

FADD:

Fas-Associated protein with Death Domain

FasR:

Fas Receptor

IAPs:

Inhibitors of Apoptosis Proteins

IHC:

Immunohistochemistry

LRIG1:

Leucine-Rich repeats and immunoglobulin-like domains protein 1

ML-IAP:

Melanoma Inhibitor of Apoptosis Protein

NCI:

National Cancer Institute

NFκB:

Nuclear Factor kappa-light-chain-enhancer of activated B cells

PMBC:

Peripheral Mononuclear Blood cells

RING:

Really Interesting New Gene

RIPK1:

Receptor-Interacting serine/threonine-protein Kinase 1

RTK:

Receptor Tyrosine Kinase

Smac:

Second Mitochondria-derived Activator of Caspases

TNF:

Tumor Necrosis Factor

TNF-alpha:

Tumor Necrosis Factor-alpha

TNFR:

Tumor Necrosis Factor Receptor

TRADD:

TNFR Associated DEATH Domain

TRAF:

TNF Receptor Associated Factor

TRAIL:

TNF Related Apoptosis-Inducing Ligand

UBA:

Ubiquitin-Associated domain

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Acknowledgments

We are grateful for the financial support from the Breast Cancer Research Foundation, the Prostate Cancer Foundation, the Department of Defense Prostate Cancer Program (W81XWH-04-1-0213), Ascenta Therapeutics, and the National Cancer Institute, NIH (5R01CA109025 and 5R01CA127551). We thank Dr. G.W.A. Milne for his critical reading of the manuscript and Ms. Karen Kreutzer for her excellent secretarial assistance.

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  1. Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA

    Shaomeng Wang, Longchuan Bai, Jianfeng Lu, Liu Liu, Chao-Yie Yang & Haiying Sun

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  1. Shaomeng Wang
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Correspondence to Shaomeng Wang.

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Wang, S., Bai, L., Lu, J. et al. Targeting Inhibitors of Apoptosis Proteins (IAPs) For New Breast Cancer Therapeutics. J Mammary Gland Biol Neoplasia 17, 217–228 (2012). https://doi.org/10.1007/s10911-012-9265-1

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