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Targeting the mitochondrial apoptotic pathway: a preferred approach in hematologic malignancies?

期刊

CELL DEATH & DISEASE
卷 5, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2014.61

关键词

apoptosis; BH3 mimetics; Bcl-2 targeting

资金

  1. Deutsche Forschungsgemeinschaft (DFG) [KFO 286-RP3, SFB 832-A9]
  2. Koln Fortune Program/Faculty of Medicine, University of Cologne

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Acquired resistance toward apoptosis represents one of the hallmarks of human cancer and a major cause of the inefficacy of most anticancer treatment regimens. Based on its ability to inhibit apoptosis, the B-cell lymphoma/leukemia 2 (Bcl-2) protein family has garnered the most attention as a promising therapeutic target in cancer. Accordingly, efforts have lately been focused on the development of drugs targeting Bcl-2 proteins with considerable therapeutic success, particularly in hematologic malignancies. Here, we review the previous studies and highlight the pivotal role of the Bcl-2 protein family in the homeostasis of hematologic tissue compartment. This knowledge provides more insight into why some cancers are more sensitive to Bcl-2 targeting than others and will foster the clinical evaluation of Bcl-2-targeting strategies in cancer by avoiding severe on-target side effects in the development of healthy tissues.

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