Targeting Multiple Arms of the Apoptotic Regulatory Machinery

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Bibliographic Information

Published
2007-04-01
DOI
  • 10.1158/0008-5472.can-07-0082
Publisher
American Association for Cancer Research (AACR)

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<jats:title>Abstract</jats:title> <jats:p>ABT-737 targets Bcl-2/Bcl-xL but not Mcl-1, which confers resistance to this novel agent. Here, we summarize recent findings indicating that Mcl-1 represents a critical determinant of ABT-737 sensitivity and resistance, and that Mcl-1 down-regulation by various pharmacologic agents or genetic approaches dramatically increases ABT-737 lethality in diverse malignant cell types. These findings also show that the multidomain proapoptotic proteins Bax and Bak play important functional roles in ABT-737–mediated apoptosis, and that Bak activation is essential in potentiation of ABT-737 lethality by agents that down-regulate Mcl-1. Collectively, these findings suggest a novel therapeutic strategy targeting multiple arms of the apoptotic machinery. [Cancer Res 2007;67(7):2908–11]</jats:p>

Journal

  • Cancer Research

    Cancer Research 67 (7), 2908-2911, 2007-04-01

    American Association for Cancer Research (AACR)

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