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Antagonists of IAP proteins as cancer therapeutics

  • Jasmin N. Dynek
    • ,
  • Domagoj Vucic

      Affiliations

    • Corresponding Author InformationCorresponding author. Address: Department of Protein Engineering, Genentech, Inc., 1 DNA Way, M/S 40, South San Francisco, CA 94080, USA. Tel.: +1 650 225 8839; fax: +1 650 225 6127.

Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080, USA

Received 6 May 2010; received in revised form 24 June 2010; accepted 25 June 2010. published online 04 August 2010.
Corrected Proof

Abstract 

Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by blocking apoptosis, modulating signal transduction, and affecting cellular proliferation. Through their interactions with inducers and effectors of apoptosis IAP proteins can effectively suppress apoptosis triggered by diverse stimuli including death receptor signaling, irradiation, chemotherapeutic agents, or growth factor withdrawal. Evasion of apoptosis, in part due to the action of IAP proteins, enhances resistance of cancer cells to treatment with chemotherapeutic agents and contributes to tumor progression. Additionally, IAP genes are known to be subject to amplification, mutation, and chromosomal translocation in human malignancies and autoimmune diseases. In this review we will discuss the role of IAP proteins in cancer and the development of antagonists targeting IAP proteins for cancer treatment.

Keywords: IAP, Antagonist, Apoptosis, XIAP, c-IAP, SMAC, TNF

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PII: S0304-3835(10)00336-8

doi:10.1016/j.canlet.2010.06.013

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