Document Detail


Ixabepilone: targeting betaIII-tubulin expression in taxane-resistant malignancies.
MedLine Citation:
PMID:  19139109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microtubule-targeting agents, such as taxanes and epothilones, block mitosis and cell proliferation by targeting the dynamics of the cytoskeleton. The taxanes are widely used for treatment of various malignancies, but primary and acquired resistance to chemotherapy remains a significant clinical concern. Class I, II, III, IV, and V beta-tubulin isotypes are expressed in human tumors. Overexpression of the betaIII-tubulin isotype is one mechanism that can render tumor cells resistant to taxanes. The relative expression of betaIII-tubulin correlates with clinical outcomes in several tumor types, including breast cancer, non-small cell lung cancer, and ovarian cancer. A novel analogue of epothilone B, ixabepilone, has recently been approved in combination with capecitabine for the treatment of patients with anthracycline- and taxane-resistant locally advanced or metastatic breast cancer and as monotherapy in patients whose tumors are resistant or refractory to an anthracycline, a taxane, and capecitabine. The significant antitumor activity of ixabepilone in taxane-resistant tumors may be related to its preferential suppression of the dynamic instability of alpha/betaIII-microtubules in cells expressing high levels of betaIII-tubulin.
Authors:
Charles Dumontet; Mary Ann Jordan; Francis F Y Lee
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  8     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-13     Completed Date:  2009-02-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-25     Citation Subset:  IM    
Affiliation:
Unité Institut National de la Sante et de la Recherche Medicale 590, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France. charles.dumontet@chu-lyon.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Bridged Compounds / therapeutic use*
Drug Resistance, Neoplasm / drug effects*
Epothilones / therapeutic use*
Humans
Neoplasms / drug therapy*,  metabolism*
Taxoids / therapeutic use*
Treatment Outcome
Tubulin / classification,  metabolism*
Chemical
Reg. No./Substance:
0/Bridged Compounds; 0/Epothilones; 0/Taxoids; 0/Tubulin; 1605-68-1/taxane; 219989-84-1/ixabepilone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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