Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells

Wen Gao, Michael Wang, Li Wang, Haibo Lu, Shuhong Wu, Bingbing Dai, Zhishuo Ou, Liang Zhang, John V. Heymach, Kathryn A. Gold, John Minna, Jack A. Roth, Wayne L. Hofstetter, Stephen G. Swisher, Bingliang Fang

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Abstract

Ibrutinib, which irreversibly inhibits Bruton tyrosine kinase, was evaluated for antitumor activity in a panel of non-small cell lung cancer (NSCLC) cell lines and found to selectively inhibit growth of NSCLC cells carrying mutations in the epidermal growth factor receptor (EGFR) gene, including T790M mutant and erlotinib-resistant H1975 cells. Ibrutinib induced dose-dependent inhibition of phosphor-EGFR at both Y1068 and Y1173 sites, suggesting ibrutinib functions as an EGFR inhibitor. Survival was analyzed by Kaplan-Meier estimation and log-rank test. All statistical tests were two-sided. In vivo study showed that ibrutinib statistically significantly suppressed H1975 tumor growth and prolonged survival of the tumor bearing mice (n = 5 per group). The mean survival times for solvent- and erlotinib-treated mice were both 17.8 days (95% confidence interval [CI] = 14.3 to 21.3 days), while the mean survival time for ibrutinib-treated mice was 29.8 days (95% CI = 26.0 to 33.6 days, P =.008). Our results indicate that ibrutinib could be a candidate drug for treatment of EGFR-mutant NSCLC, including erlotinib-resistant tumors.

Original languageEnglish (US)
Article numberdju204
JournalJournal of the National Cancer Institute
Volume106
Issue number9
DOIs
StatePublished - Sep 1 2014

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Confidence Intervals
erbB-1 Genes
Neoplasms
Growth
PCI 32765
Cell Line
Mutation
Pharmaceutical Preparations
Erlotinib Hydrochloride

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells. / Gao, Wen; Wang, Michael; Wang, Li; Lu, Haibo; Wu, Shuhong; Dai, Bingbing; Ou, Zhishuo; Zhang, Liang; Heymach, John V.; Gold, Kathryn A.; Minna, John; Roth, Jack A.; Hofstetter, Wayne L.; Swisher, Stephen G.; Fang, Bingliang.

In: Journal of the National Cancer Institute, Vol. 106, No. 9, dju204, 01.09.2014.

Research output: Contribution to journalArticle

Gao, W, Wang, M, Wang, L, Lu, H, Wu, S, Dai, B, Ou, Z, Zhang, L, Heymach, JV, Gold, KA, Minna, J, Roth, JA, Hofstetter, WL, Swisher, SG & Fang, B 2014, 'Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells', Journal of the National Cancer Institute, vol. 106, no. 9, dju204. https://doi.org/10.1093/jnci/dju204
Gao, Wen ; Wang, Michael ; Wang, Li ; Lu, Haibo ; Wu, Shuhong ; Dai, Bingbing ; Ou, Zhishuo ; Zhang, Liang ; Heymach, John V. ; Gold, Kathryn A. ; Minna, John ; Roth, Jack A. ; Hofstetter, Wayne L. ; Swisher, Stephen G. ; Fang, Bingliang. / Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells. In: Journal of the National Cancer Institute. 2014 ; Vol. 106, No. 9.
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