Abstract 4243: EGFR inhibition causes growth delay and induces apoptosis in HPV-positive head and neck cancer

Abstract

Abstract Purpose: Cetuximab, a monoclonal antibody inhibiting the epidermal growth factor receptor (EGFR), is approved for use in the treatment of head and neck cancer (HNC). However, studies of cetuximab were performed with HPV-negative cells, clinical trials were performed without regard to HPV status, and current studies on HPV+ HNC treatment with cetuximab are contradicting. This study was performed to determine whether HPV+ HNC responds to cetuximab and to examine the mechanisms through which cetuximab affects HPV+ HNC. Methods: Four HPV+ cell lines were assessed for EGFR expression by immunoblot. Sensitivity to cetuximab was tested by examining cell proliferation and colony formation. Apoptosis was measured by caspase activation, flow cytometry for Annexin V, and immunoblot. Cell cycle was assessed by immunoblot and flow cytometry for propidium iodide stained cells. HPV+ HNC subcutaneous flank cell line xenografts and patient-derived xenografts were placed in immunocompromised mice treated with cetuximab, tumor size was measured twice weekly. Results: Cetuximab treatment resulted in significant delay in cell proliferation and significant decrease in colony formation. Cetuximab caused an increase in apoptosis in all methods measured. Also, as previously seen in HPV- cell lines, cetuximab resulted in a G1 cell cycle arrest. Using both cell line and patient-derived xenograft models of HPV+ HNCs, cetuximab resulted in significant tumor growth delay (median time to tumor quadrupling: 15 vs. 24 days, and 42 vs. 89 days, respectively). Conclusions: Epidermal growth factor receptor inhibition by cetuximab is effective in slowing proliferation and inducing apoptosis in HPV+ HNC. The proposed mechanism of action appears to be similar to that shown in HPV- HNC. These results suggest that cetuximab may play a role in the management of patients with HPV+ HNC. Citation Format: Alexandra D. Torres Law, Grace C. Blitzer, Molly A. Smith, Eric A. Armstrong, Randall J. Kimple. EGFR inhibition causes growth delay and induces apoptosis in HPV-positive head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4243. doi:10.1158/1538-7445.AM2014-4243