Document Detail


Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009.
MedLine Citation:
PMID:  19739234     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Homoharringtonine (HHT) is a natural alkaloid that is obtained from various Cephalotaxus species. The mechanism of action by which HHT exerts its antitumor activity is through inhibition of protein synthesis and promotion of apoptosis. In the 1990s, HHT proved to be significantly active as salvage therapy for patients with chronic myeloid leukemia (CML) after failure on interferon-alpha therapy. However, the remarkable success of imatinib mesylate in the treatment of CML relegated HHT to oblivion. The development of omacetaxine mepesuccinate, a subcutaneously bioavailable semisynthetic form of HHT, and its activity in imatinib-resistant CML has established this agent for the second time as a valuable option in the management of this disease. Preliminary results appear to support the use of this agent for patients who have imatinib-resistant CML, including those who carry the tyrosine kinase inhibitor-insensitive mutation that exchanges the amino acids threonine and isoleucine at position 315 (the T315I mutation). In this article, the authors discuss the current data on omacetaxine and the prospects of this agent to be integrated into the state-of-the-art treatment algorithms for CML.
Authors:
Alfonso Quint??s-Cardama; Hagop Kantarjian; Jorge Cortes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cancer     Volume:  115     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2010-01-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5382-93     Citation Subset:  AIM; IM    
Copyright Information:
(c) 2009 American Cancer Society.
Affiliation:
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. aquintas@mdanderson.org
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Antineoplastic Agents, Phytogenic / therapeutic use*
Clinical Trials as Topic
Drug Discovery
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Harringtonines / chemistry,  therapeutic use*
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  genetics
Piperazines / therapeutic use
Pyrimidines / therapeutic use
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Harringtonines; 0/Piperazines; 0/Pyrimidines; 152459-95-5/imatinib; 26833-87-4/homoharringtonine

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