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Targeting the ubiquitin-proteasome pathway in cancer therapy

kekechong 添加于 2010-6-24 10:34 | 646 次阅读 | 0 个评论

作者
Ishii Y, Waxman S, Germain D
摘要
The ubiquitin-proteasome pathway plays a central role in the degradation of proteins involved in several pathways including the cell cycle, cellular proliferation and apoptosis. Bortezomib is the first proteasome inhibitor to enter clinical use, and received approval by the Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma, therefore validating inhibition of the proteasome as an anticancer target. The approval of Bortezomib was based on a large, international, multicenter phase III trial showing its efficacy and safety compared with conventional therapy. Preclinical data also demonstrates the synergistic effect of bortezomib with other chemotherapeutic agents and its ability to overcome drug resistance. Since then several other proteasome inhibitors have been developed. The anti-tumor activities of bortezomib have been attributed to its effect on pro-apoptotic pathways including the inhibition of NF-kappaB and induction of endoplasmic reticulum stress. However, the molecular mechanisms are not fully understood. In this review, we will summarize the molecular mechanism of apoptosis by bortezomib.
详细资料
- 关键词: Animals; Antineoplastic Agents/therapeutic use; Apoptosis/drug effects; Boronic Acids/therapeutic use; Cyclin D1/biosynthesis; Humans; Multiple Myeloma/drug therapy; Neoplasms/*drug therapy; Proteasome Endopeptidase Complex/antagonists & inhibitors/*physiology; Pyrazines/therapeutic use; Ubiquitin/*physiology
- 文献种类: Journal Article
- 期刊名称: Anti-Cancer Agents in Medicinal Chemistry
- 期刊缩写: Anticancer Agents Med Chem
- 期卷页: 2007年第7卷第3期 359-365页
- 地址: Division of Hematology/Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
- ISBN: 1871-5206
- 备注:PMID:17504161
学科领域生物医药 » 基础医学
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