| | |  | | | | Record from Web of Science® | | | | | | |
| A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib |
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| Author(s): Chauhan D, Catley L, Li GL, Podar K, Hideshima T, Velankar M, Mitsiades C, Mitsiades N, Yasui H, Letai A, Ovaa H, Berkers C, Nicholson B, Chao TH, Neuteboom STC, Richardson P, Palladino MA, Anderson KC |
| Source: CANCER CELL Volume: 8 Issue: 5 Pages: 407-419 Published: NOV 2005 |
| Times Cited: 188 References: 39 |
| Abstract: Bortezomib therapy has proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM); however, prolonged treatment is associated with toxicity and development of drug resistance. Here, we show that the novel proteasome inhibitor NPI-0052 induces apoptosis in MM cells resistant to conventional and Bortezomib therapies. NPI-0052 is distinct from Bortezomib in its chemical structure, effects on proteasome activities, mechanisms of action, and toxicity profile against normal cells. Moreover, NPI-0052 is orally bioactive. In animal tumor model studies, NPI-0052 is well tolerated and prolongs survival, with significantly reduced tumor recurrence. Combining NPI-0052 and Bortezomib induces synergistic anti-MM activity. Our study therefore provides the rationale for clinical protocols evaluating NPI-0052, alone and together with Bortezomib, to improve patient outcome in MM. |
| Document Type: Article |
| Language: English |
| Reprint Address: Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA |
Addresses:
1. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA
2. Nereus Pharmaceut, San Diego, CA 92121 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Oncology |
| IDS Number: 987FA |
| ISSN: 1535-6108 |
| DOI: 10.1016/j.ccr.2005.10.013 |
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