title: Resistance to cetuximab in EGFR-overexpressing esophageal squamous cell carcinoma xenografts due to FGFR2 amplification and overexpression.
abstract: Esophageal carcinoma is one of the most virulent malignant diseases and a major cause of cancer-related deaths worldwide. Despite improvements in surgical techniques and perioperative management and surgery combined with chemotherapy and/or radiotherapy, the prognosis of esophageal squamous cell carcinoma (ESCC) at an advanced stage remains poor. ESCC shows a relatively high incidence of EGFR (50% - 70%), and the humanized monoclonal antibody (mAb) cetuximab against EGFR has been undergoing clinical development. However, all responding patients eventually developed acquired resistance to cetuximab. In the current study, we described a cetuximab-sensitive ESCC xeongraft model that developed resistance to cetuximab as a result of FGFR2 gene amplification and overexpression. Inhibition of FGFR2 signaling in this xenograft model restored its sensitivity to cetuximab. The antitumor effect may be induced by inhibition of AKT phosphorylation. These findings suggest that combination therapyincluding cetuximab and FGFR2 inhibition may be a promising strategy to treat ESCC.
authors.affiliation: Department of Surgery, The Third Affiliated Hospital of Jianghan University, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Pan
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zhong
authors.forename: Cai
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D064593:Heterografts; D006801:Humans; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D051497:Receptor, Fibroblast Growth Factor, Type 2; D000068818:Cetuximab