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Anti-Apoptotic Bcl-2

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Cancer Therapeutic Targets

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Abstract

The B-cell lymphoma/leukemia 2 (BCL-2) family represents a group of proteins involved in the regulation of the intrinsic (mitochondrial) apoptotic pathway. Approximately 25 members of the BCL-2 family have been grouped into three categories based on structure and function: (1) anti- apoptotic, (2) pro-apoptotic, and (3) BH3 only proteins. This chapter will focus on a family of five anti-apoptotic proteins: (1) BCL-2, (2) BCL-xL, (3) BCL-w, (4) MCL-1, and (5) A1. The decision for a cell to undergo apoptosis is regulated by the BCL-2 family of proteins. Inhibition of anti-apoptotic BCL-2 proteins is an active area of research and represents a novel pathway in cancer therapeutics. BH3 profiling is a functional assay that measures the degree to which a cancer cell is primed to undergo apoptosis by investigating how the cells evade apoptosis by three possible mechanisms: (1) inability of activator BH3-only proteins (Bim/Bid) to function, (2) loss of pro-apoptotic BCL-2 proteins (Bax/Bak), and (3) sequestration of activator BH3 proteins by anti-apoptotic BCL-2 proteins. Approaches to target BCL-2 include RNA antisense molecules (oblimersen, SPC2996); small-molecule inhibitors (venetoclax, obatoclax, ABT-737, navitoclax, AT-101); and stabilized alpha helix of BCL-2 (SAHB) peptides. These compounds are under various stages of clinical investigation in both solid and hematologic malignancies, both as single agents and in combination with other cytotoxic regimens

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Author information

Authors and Affiliations

  1. New York Presbyterian Hospital/Columbia Campus, Columbia University Medical Center, 177 Fort Washington Avenue, MHB 6GN-435, New York, NY, 10023, USA

    Stanley R Frankel

  2. Office of Hematology and Oncology Products (OHOP), U.S. Food and Drug Administration, 10903 New Hampshire Avenue, White Oak Building 22/Room 2391, Silver Spring, MD, 20993, USA

    Dow-Chung Chi

Authors
  1. Stanley R Frankel
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  2. Dow-Chung Chi
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Correspondence to Stanley R Frankel .

Editor information

Editors and Affiliations

  1. Georgetown University Div. Hematology & Oncology, Washington, District of Columbia, USA

    John L. Marshall

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© 2013 Springer Science+Business Media New York

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Frankel, S.R., Chi, DC. (2013). Anti-Apoptotic Bcl-2. In: Marshall, J. (eds) Cancer Therapeutic Targets. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6613-0_56-3

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  • DOI: https://doi.org/10.1007/978-1-4614-6613-0_56-3

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  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6613-0

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