Influence of epidermal growth factor receptor expression on the cetuximab and panitumumab response rates of head and neck carcinoma cells

J Craniomaxillofac Surg. 2014 Oct;42(7):1322-8. doi: 10.1016/j.jcms.2014.03.018. Epub 2014 Apr 2.

Abstract

Objectives: To examine the impact of epidermal growth factor receptor (EGFR) expression level on the efficacy of monoclonal antibodies against the EGFR.

Methods: In four human head and neck carcinoma cell lines, epidermal growth factor expression was knocked down by lentiviral RNA interference. Next, the efficacies of cetuximab and panitumumab at concentrations of 4, 40, and 400 μg/ml were measured by real time cell analysis for a 48-h duration. Finally, the different response rates to the drugs were statistically analyzed.

Results: The lentiviral EGFR knockdown efficiency ranged from 18 to 54 % across all of the cell lines. All original cell lines exhibited rather poor or inverse responses with regard to EGFR-AB treatment. In contrast, inhibiting EGFR expression in the same cell lines yielded statistically significant better responses to cetuximab or panitumumab treatment.

Conclusions: The cell lines used in this study responded poorly to cetuximab and panitumumab. Better anti-EGFR treatment efficacy was related to lower EGFR expression in head and neck cancer cell lines. These findings might influence the selection of patients to receive cetuximab and panitumumab treatment for head and neck cancer.

Keywords: Cetuximab; EGFR; HNSCC; Knockdown; Panitumumab.

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma / drug therapy
  • Carcinoma / pathology*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cetuximab / pharmacology*
  • Cetuximab / therapeutic use
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / drug effects*
  • Flow Cytometry / methods
  • Gene Knockdown Techniques
  • Genetic Vectors / genetics
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / pathology
  • Lentivirus / genetics
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / pathology
  • Panitumumab
  • RNA Interference
  • RNA, Small Interfering
  • Tongue Neoplasms / drug therapy
  • Tongue Neoplasms / pathology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • RNA, Small Interfering
  • Panitumumab
  • ErbB Receptors
  • Cetuximab