期刊
BRITISH JOURNAL OF CANCER
卷 95, 期 8, 页码 961-965出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6603406
关键词
protein degradation; proteasomes; multiple myeloma; novel therapy; apoptosis; drug resistance
类别
资金
- NCI NIH HHS [CA 78373, R01 CA 50947, P50 CA100707, CA 100707] Funding Source: Medline
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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