Expression of BRAK/CXCL14 is a marker for gefitinib responsiveness of human head and neck squamous cell carcinoma

LB-112

Given the biological importance of the epidermal growth factor receptor (EGFR) in cancer development and progression, EGFR inhibitors have emerged as promising novel therapeutics. Gefitinib is the first drug that has been developed for molecular targeting therapy for EGFR and has been successfully applied in non-small cell lung carcinoma patients expressing mutated EGFRs. But these mutations are rare in the esophageal carcinoma and head and neck squamous cell carcinoma (HNSCC). Here we show that treatment of HNSCC cells with gefitinib attenuated the EGF-induced decrease in the expression of the chemokine BRAK/CXCL14 in vitro and, furthermore, that oral administration of the drug suppressed (P value <0.01) the increase in the tumor volume of xenografts in vivo, along with causing a concomitant increase in BRAK expression in the transplanted HNSCC cells. Although gefitinib administration increased the apoptotic index in control (Si-Scrambled-treated) tumor cells (P value <0.05) concomitant with suppression of the tumor volume, it did not show such an efficacy in tumor cells with siRNA-mediated BRAK knock down. These data identify a new mechanism of gefitinib action, i.e., a reduction in tumor volume through induction of BRAK expression in tumor cells in vivo. Our data also indicate that induction of BRAK expression by the treatment with gefitinib in vitro may be a very useful new approach to screen for gefitinib-responsive cancer patients with HNSCC.