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lüll Targeting BCL-2-related proteins in cancer therapy Manion MK; Hockenbery DMCancer Biol Ther 2003[Jul]; 2 (4 Suppl 1): S105-14The 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.|Apoptosis[MESH]|Cell Line, Tumor[MESH]|Clinical Trials as Topic[MESH]|Cytochromes c/metabolism[MESH]|Humans[MESH]|Mitochondria/metabolism[MESH]|Models, Biological[MESH]|Models, Chemical[MESH]|Neoplasms/*drug therapy/pathology[MESH]|Oligonucleotides, Antisense/pharmacology[MESH]|Peptides/chemistry[MESH]|Protein Structure, Tertiary[MESH]|Proto-Oncogene Proteins c-bcl-2/*metabolism[MESH]|bcl-X Protein[MESH] |