RT Journal Article SR Electronic T1 Overexpressed HER2 in NSCLC is a Possible Therapeutic Target of EGFR Inhibitors JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4155 OP 4161 VO 31 IS 12 A1 NOBUYUKI ISE A1 KAZUYA OMI A1 DAISUKE NAMBARA A1 SHIGEKI HIGASHIYAMA A1 KATSUTOSHI GOISHI YR 2011 UL http://ar.iiarjournals.org/content/31/12/4155.abstract AB Background: “Oncogene addiction” is a concept in which tumor cells exhibit dependence on certain oncogene(s) for their sustained proliferation and survival, thus providing the rationale for molecular targeted therapies. Cancer cells addicted to epidermal growth factor receptor (EGFR) bear activated mutations in the EGFR gene, and these mutations are used as the markers for predicting carcinomas susceptible to EGFR inhibitors such as gefitinib and erlotinib. However, other unknown mechanisms underlying susceptibility to EGFR inhibitors have also been suggested. Materials and Methods: The susceptibility of non-small-cell lung cancer (NSCLC) cell lines to EGFR inhibitors and the pattern of their oncogene addiction was examined. The effect of EGFR inhibitors on the activation of the oncogene was analyzed. The possible use of the oncogene protein expression as a biomarker was assessed. Results: HER2 addicted, non-EGFR expressing NSCLC cell line NCI-H2170 was susceptible to EGFR inhibitors. EGFR inhibitor treatment led to markedly decreased phosphorylation levels of activated HER2 and its downstream effector AKT. Furthermore, the soluble form of HER2 was secreted by NCI-H2170 cells and was positively detected in the blood of xenografted mice. Conclusion: HER2 seems to be a valid therapeutic target of EGFR inhibitors in HER2-addicted lung carcinomas, and soluble HER2 may be an effective biomarker to guide the appropriate treatment of such cancer cells.