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Therapeutic potential of a peptide targeting BCL-2 cell guardians in cancer
Jerry M. Adams
Jerry M. Adams
Published May 24, 2012
Citation Information: J Clin Invest. 2012;122(6):1965-1967. https://doi.org/10.1172/JCI64120.
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Therapeutic potential of a peptide targeting BCL-2 cell guardians in cancer

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Abstract

A promising approach to cancer therapy is to elicit apoptosis with “BH3 mimetic” drugs, which target proteins of the BCL-2 family. As of yet, however, such drugs can target only certain BCL-2 family proteins. Hence, in this issue of the JCI, LaBelle et al. assess instead the therapeutic potential of a “stapled” BH3 peptide from the BIM protein, which inactivates all its prosurvival relatives. The peptide killed cultured hematologic tumor cells and abated growth of a leukemia xenograft, without perturbing the hematopoietic compartment. Hence, such peptides might eventually provide a new way to treat refractory leukemias.

Authors

Jerry M. Adams

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Figure 1

Contrasting pharmacologic strategies for reactivating cell death in refractory hematologic malignancies with a BH3 mimetic compound or a stabilized BIM BH3 peptide.

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Contrasting pharmacologic strategies for reactivating cell death in refr...
(A) Because the BH3 mimetic ABT-263 effectively neutralizes BCL-2 and BCL-xL but not MCL-1, it is very effective as a single agent for malignancies in which BCL-2 or BCL-xL is the dominant guardian restraining BAX but not those in which MCL-1 can still restrain BAX and prevent apoptosis. (B) LaBelle et al. have investigated the apoptotic potential of a hydrocarbon stapled BH3 peptide (SAHB) from the protein BIM, which broadly targets BCL-2 family proteins and can directly activate BAX as well as neutralize all its prosurvival relatives. In principle, the BIM SAHB could be more potent than a more specific BH3 mimetic, and, indeed, it proved to augment killing of hematologic tumor cells refractory to ABT-263, suggesting that such peptides might have potential as anticancer therapeutics.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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