期刊
CURRENT CANCER DRUG TARGETS
卷 14, 期 6, 页码 537-548出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568009614666140723113139
关键词
Constitutive proteasome; immunoproteasome; mantle cell lymphoma; multiple myeloma; small molecule inhibitors; subunit-selective inhibitor
类别
资金
- National Institutes of Health [R01 CA128903]
Remarkable successes with the FDA-approved proteasome inhibitors bortezomib (Velcade (R)) and carfilzomib (Kyprolis (R)) have proved that the proteasome is an effective target for the treatment of multiple myeloma. In other hematological malignancies, however, clinical trials of proteasome-targeting drugs have shown generally disappointing results to date. Additionally, existing proteasome inhibitors have significant issues with toxicity, poor response rate, and the emergence of resistance for many patients. A new generation of small-molecule therapies specifically targeting the immunoproteasome may have the potential to overcome the drawbacks of bortezomib and carfilzomib in multiple myeloma and to bring significant benefits of proteasome inhibitor therapies to many more patients. In this article, we describe the potential of the immunoproteasome as a therapeutic target for hematological malignancies and the recent progress in the development of useful immunoproteasome inhibitors.
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