Fennell D A, Chacko A, Mutti L
Thoracic Oncology Research Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland, UK.
Oncogene. 2008 Feb 21;27(9):1189-97. doi: 10.1038/sj.onc.1210744. Epub 2007 Sep 10.
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.
硼替佐米（万珂，PS341）于2003年获批，是首个用于治疗多发性骨髓瘤的20S蛋白酶体抑制剂，目前正在多种实体瘤中进行临床评估。其癌细胞毒性的潜在机制很复杂。越来越多的证据表明，蛋白酶体抑制依赖性的BCL-2家族调节是一个关键要求。特别是，仅含BH3结构域的蛋白质BIK、NOXA和BIM的稳定似乎对于实现BAX和BAK依赖性细胞死亡至关重要。本文对这些机制进行了综述，并强调了其对新型药物良好相互作用的意义。
