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IAP Family of Proteins as Therapeutic Targets for Acute Myeloid Leukemia

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Targeted Therapy of Acute Myeloid Leukemia

Part of the book series: Current Cancer Research ((CUCR))

Abstract

The inhibitor of apoptosis protein (IAP) family is a group of proteins that are critical regulators of cell survival. They also play roles in cell cycle, cell signaling, and cell migration. The expression of many IAPs is deregulated in acute myeloid leukemia (AML) and other malignant cells and contributes to tumor formation, progression, and maintenance; drug resistance and treatment failure; and poor prognosis. In the last decade, abundant knowledge has been accumulated regarding the structure, expression, regulation, function, and mechanism of action of IAPs, which has led to significant progress in developing strategies to antagonize IAPs. Many candidate compounds have been investigated and tested in the preclinical setting, and some of them have moved to clinical development. This chapter highlights current knowledge of the expression and roles of IAPs in AML and discusses current strategies exploiting IAPs as therapeutic targets for AML.

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Authors and Affiliations

  1. Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd # 448, 77030-4009, Houston, TX, USA

    Bing Z. Carter Ph.D. & Michael Andreeff M.D., Ph.D.

Authors
  1. Bing Z. Carter Ph.D.
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  2. Michael Andreeff M.D., Ph.D.
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Correspondence to Bing Z. Carter Ph.D. .

Editor information

Editors and Affiliations

  1. Dept. Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Michael Andreeff

Conclusion

Conclusion

In recent years, IAPs have emerged as promising targets for cancer therapy, including AML treatment, because of their elevated expression, their roles in cancer cell survival and drug resistance , and their association with poor clinical outcomes. ASOs against these proteins and several small-molecule IAP antagonists, in particular SMAC mimetics, have been developed and are currently being evaluated in clinical trials in AML and other malignancies. Future studies should emphasize better understanding of other natural IAP inhibitors and their interaction with IAPs to develop improved IAP antagonists and rationally combine SMAC mimetics with other therapeutic agents to maximize apoptotic induction and minimize drug resistance and microenvironmental protection to leukemic cells. We hope to see all these research efforts translate into better treatment strategies and improved outcomes for patients with AML in the near future. IAP-based targeted therapy holds promise for enhancing and improving current chemotherapies for AML.

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© 2015 Springer-Verlag New York

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Carter, B., Andreeff, M. (2015). IAP Family of Proteins as Therapeutic Targets for Acute Myeloid Leukemia. In: Andreeff, M. (eds) Targeted Therapy of Acute Myeloid Leukemia. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1393-0_5

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  • DOI: https://doi.org/10.1007/978-1-4939-1393-0_5

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1392-3

  • Online ISBN: 978-1-4939-1393-0

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