Proteasome inhibition in multiple myeloma: Therapeutic implication

被引:112
作者
Chauhan, D [1 ]
Hideshima, T [1 ]
Anderson, KC [1 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA
关键词
plasma call neoplasm; proteasomes; growth; survival; apoptosis; drug-resistance;
D O I
10.1146/annurev.pharmtox.45.120403.100037
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Normal cellular functioning requires processing of proteins regulating cell cycle, growth, and apoptosis. The ubiquitin-proteasome pathway (UBP) modulates intracellular protein degradation. Specifically, the 26S proteasome is a multienzyme protease that degrades misfolded or redundant proteins; conversely, blockade of the proteasomal degradation pathways results in accumulation of unwanted proteins and cell death. Because cancer cells are more highly proliferative than normal cells, their rate of protein translation and degradation is also higher. This notion led to the development of proteasome inhibitors as therapeutics in cancer. The FDA recently approved the first proteasome inhibitor bortezomib (Velcade(TM)), formerly known as PS-341, for the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Ongoing studies are examining other novel proteasome inhibitors, in addition to bortezomib, for the treatment of MM and other cancers.
引用
收藏
页码:465 / 476
页数:14
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