1999
DOI: 10.1200/jco.1999.17.6.1786
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Abstract: We have identified beta-tubulin gene mutations as a strong predictor of response to the antitubulin drug paclitaxel; these mutations may represent a novel mechanism of resistance and should be examined prospectively in future trials of taxane-based therapy in NSCLC.

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Cited by 268 publications
(160 citation statements)
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“…Interestingly, the expression levels of the various isotypes have been reported to be tissue specific and different in normal and pathological tissues. 2 In normal epithelial cells Class I b-tubulin is largely represented while Class II do not 2 ; conversely, in some cancer types, such as non small cell lung carcinoma 3 and ovarian cancer, 4 Classes I and IV b-tubulin are differently expressed showing that tumors of different origin could be characterized by a different tubulin pattern.…”
mentioning
confidence: 99%
“…Interestingly, the expression levels of the various isotypes have been reported to be tissue specific and different in normal and pathological tissues. 2 In normal epithelial cells Class I b-tubulin is largely represented while Class II do not 2 ; conversely, in some cancer types, such as non small cell lung carcinoma 3 and ovarian cancer, 4 Classes I and IV b-tubulin are differently expressed showing that tumors of different origin could be characterized by a different tubulin pattern.…”
mentioning
confidence: 99%
“…However, no HM40 mutations were identified in patient samples or nondrug-selected human cancer cell lines (Kelley et al, 2001;Sˇale et al, 2002;Tsurutani et al, 2002). Previously, tubulin mutations had been described in NSCLC patients (Monzo et al, 1999); however, when the sequences were checked using BLAST, many of the substitutions were found to correspond to pseudogenes (Monzo et al, 2002). Using quantitative PCR, the expression of HM40 was found to be the predominant b-tubulin isotype in human ovarian carcinoma xenografts, and increased expression of btubulin class III (Hb4) correlated with paclitaxel resistance in ovarian cancer cell lines (Nicoletti et al, 2001).…”
mentioning
confidence: 99%
“…One mechanism that is likely to cause Taxol resistance is thought to involve alterations in microtubule structure and͞or function (12). For example, drug-resistant cancer cell lines and human tumor tissues have been shown to harbor tubulin gene mutations, alterations in total tubulin content, altered microtubule polymer levels, altered expression of tubulin isotypes, and altered microtubule-associated protein expression (13)(14)(15)(16)(17)(18)(19)(20). All of these modifications in tubulin could, directly or indirectly, influence microtubule dynamics.…”
mentioning
confidence: 99%