Oral

[O1-D-PM1-05] Expression of the chemokine CXCL14 is a predictive biomarker for cetuximab-dependent tumor suppression

〇Ryu-Ichiro Hata¹ (1. Kanagawa Dent Univ Grad Sch Dent)

Keywords:セツキシマブ、抗癌剤の作用機作、CXCL14

[Objective] Cetuximab (Erbitux), a monoclonal antibody against epidermal growth factor receptor (EGFR), has been applied successfully in some patients with colorectal cancer and head and neck squamous cell carcinoma (HNSCC). However, for effective treatment, it is important to first identify cetuximab-responsive patients. In unresponsive patients, mutations in the signaling molecules downstream of EGFR have been implicated as causative factors. [Methods] Here, we compared CXCL14 (a chemokine gene) expression in cetuximab-responsive (HSC-3) and -resistant (YCU-H891) HNSCC cells. [Results] Both cell types did not exhibit the reported mutations. Treatment of tumour burden with cetuximab, only mice inoculated with HSC-3 cells but not with YCU- H891 cells showed suppression of growth of tumours. YCU-H891 cells exhibited hypermethylation in the CXCL14 promoter region and demethylation of this promoter region by treatment with 5-aza-2’-deoxycytidine restored CXCL14 mRNA expression in cell culture experiment, concomitant with in vivo tumour-growth suppression with cetuximab. Finally, YCU-H891 cells were engineered to express CXCL14 ectopically in the presence of doxycycline. Cetuximab-dependent tumor suppression was observed in vivo upon concomitant doxycycline administration. [Conclusion]
These results indicate that CXCL14 expression is a predictive biomarker for cetuximab-dependent tumor suppression.