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

Mingqiang Ren, Mei Hong, Gentao Liu, Hongjin Wang, Vijaykumar Surendrakant Patel, Paul Williams Biddinger, Maria J Silva, John Kenneth Cowell, Zhonglin Hao

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2181-2190
Number of pages10
JournalOncology Reports
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2013

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Receptor, Fibroblast Growth Factor, Type 1
Non-Small Cell Lung Carcinoma
Growth
Lung Neoplasms
ponatinib
Cell Line
Therapeutics
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Neoplasms

Keywords

  • Fibroblast growth factor receptor 1
  • Non-small cell lung cancer
  • Ponatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Novel FGFR inhibitor ponatinib suppresses the growth of non-small cell lung cancer cells overexpressing FGFR1. / Ren, Mingqiang; Hong, Mei; Liu, Gentao; Wang, Hongjin; Patel, Vijaykumar Surendrakant; Biddinger, Paul Williams; Silva, Maria J; Cowell, John Kenneth; Hao, Zhonglin.

In: Oncology Reports, Vol. 29, No. 6, 01.06.2013, p. 2181-2190.

Research output: Contribution to journalArticle

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