BCL-2 family regulation by the 20S proteasome inhibitor bortezomib.


Bortezomib (Velcade, PS341) was licensed in 2003 as a first-in-class 20S proteasome inhibitor indicated for treatment of multiple myeloma, and is currently being evaluated clinically in a range of solid tumours. The mechanisms underlying its cancer cell toxicity are complex. A growing body of evidence suggests proteasome inhibition-dependent regulation of the BCL-2 family is a critical requirement. In particular, the stabilization of BH3-only proteins BIK, NOXA and BIM, appear to be essential for effecting BAX- and BAK-dependent cell death. These mechanisms are reviewed and the implications for favourable novel drug interactions are highlighted.

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@article{Fennell2008BCL2FR, title={BCL-2 family regulation by the 20S proteasome inhibitor bortezomib.}, author={D A Fennell and A Chacko and L Mutti}, journal={Oncogene}, year={2008}, volume={27 9}, pages={1189-97} }