Retracted: Response to dual blockade of epidermal growth factor receptor (EGFR) and cycloxygenase-2 in nonsmall cell lung cancer may be dependent on the EGFR mutational status of the tumor

Authors

  • Shirish M. Gadgeel MD,

    Corresponding author
    1. Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
    • Division of Hematology/Oncology, Karmanos Cancer Center, Wayne State University, 4100 John R St., 4 HWCRC, Detroit, MI 48201===

    Search for more papers by this author
    • Fax: (313) 576–8699

    • Dr. Gadgeel has received research support from Astra-Zeneca, OSI Pharmaceuticals, and Pfizer.

  • Shadan Ali MS,

    1. Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
    Search for more papers by this author
  • Philip A. Philip MD,

    1. Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
    Search for more papers by this author
    • Dr. Philip has received research support from OSI Pharmaceuticals.

  • Fakhara Ahmed MS,

    1. Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
    Search for more papers by this author
  • Antoinette Wozniak MD,

    1. Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
    Search for more papers by this author
    • Dr. Wozniak is a member of the Advisory Board for Astra-Zeneca and has received research support from OSI Pharmaceuticals.

  • Fazlul H. Sarkar PhD

    1. Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
    Search for more papers by this author

Errata

This article is corrected by:

  1. Errata: Retraction Volume 122, Issue 20, 3248, Article first published online: 29 July 2016

  • Gefitinib was received from Astra-Zeneca and erlotinib was received from OSI Pharmaceuticals.

Abstract

BACKGROUND.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated clinical benefit in patients with nonsmall cell lung cancer (NSCLC), particularly those with tumors that have EGFR-TK domain mutations. Moreover, the EGFR and cyclooxygenase (COX)-2 pathways are known to enhance the procarcinogenic effects of each other in different tumor types. Therefore, it was hypothesized that tumor EGFR mutation status may influence the effectiveness of simultaneous EGFR and COX-2 inhibition in patients with NSCLC.

METHODS.

Three NSCLC cell lines with varying EGFR mutation status and sensitivities to EGFR-TKIs were selected: H3255 (L858R), H1650 (del E746-A750), and H1781 (wild-type EGFR). Cells were treated with erlotinib, gefitinib, or celecoxib alone, and the combination of both EGFR-TKI inhibitors with celecoxib. Cell survival and apoptosis was assessed and correlated with the expression of COX-2, EGFR, pEGFR, Akt, pAkt, expression, and derived prostaglandin E2 (PGE2).

RESULTS.

Celecoxib by itself was found to have no effects on cell growth or apoptosis in any of the cell lines. Erlotinib and gefitinib inhibited cell growth and induced apoptosis in both mutant cell lines and did so in H1781 cells at 10-fold higher concentrations. Celecoxib when added to erlotinib or gefitinib significantly enhanced the antiproliferative and proapoptotic effects in both mutant cell lines but had no additional effects in H1781 cells. Greater down-regulation of COX-2, EGFR, pEGFR, Akt, pAkt, and PGE2 was found when H3255 cells were treated with the combination compared with any of the single agents alone.

CONCLUSIONS.

The results of the current study demonstrate that the effectiveness of the addition of celecoxib to an EGFR-TKI is significantly greater in NSCLC cells with EGFR mutations, which is likely due to more complete inhibition of both pathways. Cancer 2007. © 2007 American Cancer Society.

Ancillary