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Rational Design of Therapeutics Targeting the BCL-2 Family: Are Some Cancer Cells Primed for Death but Waiting for a Final Push?

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Programmed Cell Death in Cancer Progression and Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 615))

A mechanism for circumventing apoptosis prevalent in many cancer cells is the overexpression of antiapoptotic BCL-2 family members. Upregulated expression of BCL-2 may be required to permit ongoing death signaling without a cellular response. Therefore, antagonizing BCL-2 function may cause death in many cancer cells. The selection for expression of BCL-2 or other antiapoptotic proteins during oncogenesis may derive from these proteins' ability to bind and sequester proapoptotic BH3-only proteins. This situation may be advantageous from a therapeutic viewpoint because cancer cells may be distinguished from normal cells by being primed with death signals. There are several strategies currently under investigation that may lead to improved treatment of many cancers by taking advantage of these differences.

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  1. Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Dana 530B, Boston, MA 02115, USA

    Victoria Del Gaizo Moore & Anthony Letai

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Moore, V.D.G., Letai, A. (2008). Rational Design of Therapeutics Targeting the BCL-2 Family: Are Some Cancer Cells Primed for Death but Waiting for a Final Push?. In: Programmed Cell Death in Cancer Progression and Therapy. Advances in Experimental Medicine and Biology, vol 615. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6554-5_8

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