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Cancer Biol Ther. 2003 Jul-Aug;2(4 Suppl 1):S105-14.

Targeting BCL-2-related proteins in cancer therapy.

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Hockenbery Lab, Fred Hutchinson Cancer Research Center; Seattle, Washington 98109, USA.


The BCL-2 family proteins are attractive targets for drug design. As pivotal regulators of apoptotic cell death, the logic of manipulating BCL-2 functions for anti-tumor effects is perhaps the strongest for any of the molecular targets proposed for cancer therapeutics. Moreover, elevated levels of anti-apoptotic proteins have been demonstrated in virtually every type of human cancer. BCL2-specific antisense oligonucleotides have shown broad anti-cancer activities in pre-clinical models and are currently in several phase III trials. Rational drug design to manipulate the functions of these proteins has been hampered by the lack of a clear understanding of biochemical or molecular functions. Initial efforts have been centered on disrupting protein-protein interactions within the BCL-2 homology (BH) family. Substantial progress in this task has been made using molecular modeling and drug leads.

[Indexed for MEDLINE]

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