Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1

  • Authors:
    • Mingqiang Ren
    • Mei Hong
    • Gentao Liu
    • Hongjin Wang
    • Vijay Patel
    • Paul Biddinger
    • Jeane Silva
    • John Cowell
    • Zhonglin Hao
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  • Published online on: April 4, 2013     https://doi.org/10.3892/or.2013.2386
  • Pages: 2181-2190
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Abstract

Lung cancer is still the leading cause of cancer-related deaths worldwide. Identifying new oncogenic drivers and developing efficient inhibitors through molecular targeting approaches are crucial for improving therapies. The aim of this study was to investigate whether targeting fibroblast growth factor receptor 1 (FGFR1) with ponatinib inhibits the cell growth in both established and primary lung cancer cells overexpressing FGFR1. Eighty-eight non-small cell lung cancer (NSCLC) and paired normal tissue specimens were analyzed by real-time RT-PCR for FGFR1 gene expression. We identified four cell lines and two newly established primary lung cancer cultures that showed high FGFR1 expression levels, and evaluated the effect of the novel FGFR1 inhibitor ponatinib on cell growth. Approximately 50% (30 out of 59) NSCLC specimens expressed FGFR1 >2-fold compared with their adjacent normal counterparts using quantitative RT-PCR. Ponatinib treatment of established NSCLC cell lines expressing higher levels of FGFR1 resulted in marked cell growth inhibition and suppression of clonogenicity. This growth inhibition was associated with inactivation of FGFR1 and its downstream targets. FGFR1 knockdown by shRNA achieved similar results when compared to treatment with ponatinib. Furthermore, ponatinib was able to significantly inhibit the growth of primary lung cancer cultures in vitro. Our data indicate that pharmacological inhibition of FGFR1 kinase activity with ponatinib may be effective for the treatment of lung cancer patients whose tumors overexpress FGFR1.
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June 2013
Volume 29 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ren M, Hong M, Liu G, Wang H, Patel V, Biddinger P, Silva J, Cowell J and Hao Z: Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1. Oncol Rep 29: 2181-2190, 2013.
APA
Ren, M., Hong, M., Liu, G., Wang, H., Patel, V., Biddinger, P. ... Hao, Z. (2013). Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1. Oncology Reports, 29, 2181-2190. https://doi.org/10.3892/or.2013.2386
MLA
Ren, M., Hong, M., Liu, G., Wang, H., Patel, V., Biddinger, P., Silva, J., Cowell, J., Hao, Z."Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1". Oncology Reports 29.6 (2013): 2181-2190.
Chicago
Ren, M., Hong, M., Liu, G., Wang, H., Patel, V., Biddinger, P., Silva, J., Cowell, J., Hao, Z."Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1". Oncology Reports 29, no. 6 (2013): 2181-2190. https://doi.org/10.3892/or.2013.2386