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Article

Effect of PF-02341066 and radiation on non-small cell lung cancer cells

  • Authors:
    • Vasu Tumati
    • Subashri Kumar
    • Lan Yu
    • Benjamin Chen
    • Hak Choy
    • Debabrata Saha
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
  • Pages: 1094-1100
    |
    Published online on: December 18, 2012
       https://doi.org/10.3892/or.2012.2198
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Abstract

Recently, a fusion protein of echinoderm microtubule associated protein like-4 (EML4) and anaplastic lymphoma kinase (ALK) has been found in non-small cell lung cancer (NSCLC) patients. In addition, endogenous expression of phosphorylated c-Met was found to be increased in many invasive NSCLC cases. PF-02341066 (crizotinib) is a novel dual c-Met and EML4-ALK inhibitor, and preclinical studies have shown that treatment with ALK inhibitors leads to drastic tumor regression in xenograft models. A phase I trial of PF-02341066 yielded a 53% response rate and a disease control rate of 79%. We evaluated crizotinib as a potential radiation-sensitizing agent in multiple established NSCLC cell lines with varying expression levels of c-Met and EML4-ALK. The combined effect of ionizing radiation (IR) and PF-02341066 was determined by the surviving cell fraction, cell cycle distribution, apoptosis, DNA double-strand break repair in 5 NSCLC cell lines (A549, H460, H3122, H2228 and H1993) and in in vivo xenograft studies. Treatment of NSCLC cells with either PF-02341066 alone or PF-02341066 + IR did not significantly alter cellular radiosensitivity, DNA repair kinetics and cell cycle distribution; no significant enhancement of tumor growth delay was noted in response to the combined treatment of PF-02341066 + IR. EML4-ALK and c-Met inhibition leads to activation of parallel pathways that converge on Akt signaling which abrogates any radiation-sensitizing effect. Although PF-02341066 is an effective therapy able to suppress tumor growth in tumors that exhibit positivity for either EML4-ALK or c-Met, it did not affect the intrinsic radiation response of tumor cell lines. In the present study, we demonstrated that PF-02341066 did not enhance radiation sensitivity in a panel of NSCLC cell lines.
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Copy and paste a formatted citation
Spandidos Publications style
Tumati V, Kumar S, Yu L, Chen B, Choy H and Saha D: Effect of PF-02341066 and radiation on non-small cell lung cancer cells. Oncol Rep 29: 1094-1100, 2013.
APA
Tumati, V., Kumar, S., Yu, L., Chen, B., Choy, H., & Saha, D. (2013). Effect of PF-02341066 and radiation on non-small cell lung cancer cells. Oncology Reports, 29, 1094-1100. https://doi.org/10.3892/or.2012.2198
MLA
Tumati, V., Kumar, S., Yu, L., Chen, B., Choy, H., Saha, D."Effect of PF-02341066 and radiation on non-small cell lung cancer cells". Oncology Reports 29.3 (2013): 1094-1100.
Chicago
Tumati, V., Kumar, S., Yu, L., Chen, B., Choy, H., Saha, D."Effect of PF-02341066 and radiation on non-small cell lung cancer cells". Oncology Reports 29, no. 3 (2013): 1094-1100. https://doi.org/10.3892/or.2012.2198
Copy and paste a formatted citation
x
Spandidos Publications style
Tumati V, Kumar S, Yu L, Chen B, Choy H and Saha D: Effect of PF-02341066 and radiation on non-small cell lung cancer cells. Oncol Rep 29: 1094-1100, 2013.
APA
Tumati, V., Kumar, S., Yu, L., Chen, B., Choy, H., & Saha, D. (2013). Effect of PF-02341066 and radiation on non-small cell lung cancer cells. Oncology Reports, 29, 1094-1100. https://doi.org/10.3892/or.2012.2198
MLA
Tumati, V., Kumar, S., Yu, L., Chen, B., Choy, H., Saha, D."Effect of PF-02341066 and radiation on non-small cell lung cancer cells". Oncology Reports 29.3 (2013): 1094-1100.
Chicago
Tumati, V., Kumar, S., Yu, L., Chen, B., Choy, H., Saha, D."Effect of PF-02341066 and radiation on non-small cell lung cancer cells". Oncology Reports 29, no. 3 (2013): 1094-1100. https://doi.org/10.3892/or.2012.2198
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