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SMAC IAP Addiction in Cancer

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Cell Death Signaling in Cancer Biology and Treatment

Part of the book series: Cell Death in Biology and Diseases ((CELLDEATH))

Abstract

Deregulation of apoptosis is a hallmark of human cancer. Inhibitor of apoptosis proteins (IAPs) were first identified as inhibitors of caspases and apoptosis. They were later shown to play important roles in signal transduction to promote cell survival and proliferation beyond apoptosis, a function conserved in lower eukaryotes. Genetic alterations of cIAPs, as well as widespread altered expression in IAPs and their endogenous inhibitors such as SMAC, have been reported to be associated with disease progression and chemoresistance in cancer. Several strategies have been devised to target IAPs in cancer including rationally designed small-molecule IAP antagonists based on the conserved interaction between IAPs and SMAC. Known as SMAC mimetics, these agents are showing promise as novel cancer therapeutics and help reveal novel functions of IAPs.

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Acknowledgments

We are grateful to Dr. Lin Zhang for critical reading and comments, and Mrs. Laurice Vance-Carr for excellent secretarial assistance. The work in authors’ laboratory is supported in part by NIH grants CA129829, UO1-DK085570, American Cancer Society grant RGS-10-124-01-CCE, and Flight Attendant Medical Research Institute (FAMRI).

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Authors and Affiliations

  1. Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Matthew F. Brown, Kan He & Jian Yu

  2. Department of Pathology and Molecular and Cellular Pathology Graduate Training Program, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Matthew F. Brown & Jian Yu

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  1. Matthew F. Brown
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  2. Kan He
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Correspondence to Jian Yu .

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  1. Department of Medicine, University of Pittsburgh Division of Hematology/Oncology, Pittsburgh, Pennsylvania, USA

    Daniel E. Johnson

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Brown, M.F., He, K., Yu, J. (2013). SMAC IAP Addiction in Cancer. In: Johnson, D. (eds) Cell Death Signaling in Cancer Biology and Treatment. Cell Death in Biology and Diseases. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-5847-0_10

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