Journal
DRUG RESISTANCE UPDATES
Volume 8, Issue 4, Pages 205-218Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2005.06.001
Keywords
multiple myeloma; bortezomib; thalidomide; rapamycin; HDAC inhibitors; proteasome inhibitors; drug resistance
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The introduction of melphalan and prednisone 40 years ago was a significant advance in the treatment of multiple myeloma (MM). In the following decades, significant advances were few, but included landmarks, such as the introduction of VAD and autologous transplantation during the 1980s and bisphosphonates in the 1990s. Although response rates to therapy were increased, overall survival was not significantly improved. In 1999, the treatment of myeloma was revolutionized by the introduction of thalidomide. Subsequently, the development of the immunomodulatory thalidomide analogues and the proteasome inhibitor bortezomib have impacted on response rates to therapy in relapsed and refractory myeloma and are currently being evaluated as primary therapy for myeloma. Early results suggest activity in combination with standard therapy to overcome drug resistance in patients with early stage disease and are changing treatment strategies in multiple myeloma. As an increasing number of other novel therapeutics is identified and mechanisms of resistance are elucidated, combinations of these drugs will be developed to optimize new therapeutic regimens. (c) 2005 Elsevier Ltd. All rights reserved.
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