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Review
Targeting Bcl-2 Related Proteins in Cancer Therapy
Michael K. Manion and David Hockenbery
volume 2
july/august 2003 supplementPages: S105-S115
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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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.