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Review
.2015 May 30;6(15):12862-71.
doi: 10.18632/oncotarget.3868.

New dimension in therapeutic targeting of BCL-2 family proteins

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Review

New dimension in therapeutic targeting of BCL-2 family proteins

Samaher Besbes et al. Oncotarget..

Abstract

Proteins of the BCL-2 family control the mitochondrial pathway of apoptosis. Targeting these proteins proves to be an attractive strategy for anticancer therapy. The biological context is based on the fact that BH3-only members of the family are specific antagonists of prosurvival members. This prompted the identification of "BH3 mimetic" compounds. These small peptides or organic molecules indeed mimic the BH3 domain of BH3-only proteins: by selectively binding and antagonizing prosurvival proteins, they can induce apoptosis in malignant cells. Some small-molecule inhibitors of prosurvival proteins have already entered clinical trials in cancer patients and two of them have shown significant therapeutic effects. The latest developments in the field of targeting BCL-2 family proteins highlight several new antagonists of prosurvival proteins as well as direct activators of proapoptotic proteins. These compounds open up novel prospects for the development of BH3 mimetic anticancer drugs.

Keywords: BH3 mimetics; anticancer therapy; apoptosis; prosurvival protein antagonists; targeting BCL-2 family proteins.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicts of interest to declare.

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