A novel proteasome inhibitor NPI-0052 as an anticancer therapy

被引：121

作者：

Chauhan, D. ^{[1
]}

Hideshima, T. ^{[1
]}

Anderson, K. C. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA

来源：

BRITISH JOURNAL OF CANCER | 2006年 / 95卷 / 08期

关键词：

protein degradation; proteasomes; multiple myeloma; novel therapy; apoptosis; drug resistance;

D O I：

10.1038/sj.bjc.6603406

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Proteasome inhibitor Bortezomib/Velcade has emerged as an effective anticancer therapy for the treatment of relapsed and/or refractory multiple myeloma ( MM), but prolonged treatment can be associated with toxicity and development of drug resistance. In this review, we discuss the recent discovery of a novel proteasome inhibitor, NPI-0052, that is distinct from Bortezomib in its chemical structure, mechanisms of action, and effects on proteasomal activities; most importantly, it overcomes resistance to conventional and Bortezomib therapies. In vivo studies using human MM xenografts shows that NPI-0052 is well tolerated, prolongs survival, and reduces tumour recurrence. These preclinical studies provided the basis for Phase-I clinical trial of NPI-0052 in relapsed/refractory MM patients.

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收藏

页码：961 / 965

页数：5

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