Abstract 490: Different localization of epidermal growth factor receptor affects the response of Cetuximab in the irradiated NSCLC cell lines

Abstract

Abstract The overexpressed epidermal growth factor receptor (EGFR) mediates resistance of tumor cells to chemo- and radiotherapy resulting from the induction of DNA repair by DNA-PK activation. The blockage of EGFR by a specific antibody (cetuximab) or tyrosine kinase inhibitor can inhibit the nuclear import of EGFR and consequently increase cellular sensitivity to ionizing radiation. Even though cetuximab combined with radiation showed encouraging response rates in locally advanced head and neck cancer, there are negative results in a recent trials comparing cetuximab and chemotherapy to chemotherapy alone. Thus it is critical to preselect patients based on their biologic factors to predict sensitivity for combination of cetuximab and radiation. The human non-small cell lung cancer (NSCLC) cell lines, A549 and H1299 which contain wild type EGFR, were used to demonstrate the different response to cetuximab in the combination with radiotherapy. Localization of EGFR was detected by confocal microscope and radiosensitivity was measured by clonogenic assay. Treatment of cetuximab inhibited colony formation in a dose-dependent manner in A549 cell line, while did not affect that in H1299 cell line. Microscopic images revealed that EGFR localized in cytosolic fraction especially around golgi body in H1299 cell line instead of the localization in membrane fraction in A549 cell line. After irradiation nuclear EGFR was detected in A549 cell line, however EGFR did not translocate to nucleus in H1299 cell. Even though decreased EGFR expression both A549 and H1299 cell lines was detected in the combination with cetuximab and radiation, radiosensitivity was increased only in A549 cells, not in H1299 cells. Our data indicated that localization of EGFR is evident marker to determine the efficacy of cetuximab and may relate sensitivity/resistance of cells treated cetuximab in the combination with radiotherapy. We suggest that EGFR status can be used for preselection of patients to predict treatment sensitivity in the combination therapy. *Grant Support : This study was supported by a grant (A090401) of Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 490.