Gene status of head and neck squamous cell carcinoma cell lines and cetuximab‐mediated biological activities

Abstract

Cetuximab is a chimeric IgG1 monoclonal antibody that targets epidermal growth factor receptor (EGFR). Cetuximab binds to EGFR and prevents phosphorylation of EGFR. Moreover, preclinical results have shown the ability of cetuximab to induce either complement-mediated tumor cell killing (CDC) or antibody-dependent cell-mediated-cytotoxicity (ADCC). We previously reported mutation in EGFR regarding head and neck squamous cell carcinoma (HNSCC) cell lines. In the present study, we analyzed the same 16 HNSCC cell lines for mutations in KRAS, PIK3CA, BRAF and PTEN. Furthermore, we evaluated cetuximab-mediated biological activities (antiproliferative effect by the MTT assay and ADCC) regarding these cell lines. Mutations in PIK3CA and PTEN were observed in two cell lines (2 ⁄ 16, 12.5%), but no mutation was observed in KRAS and BRAF. The antiproliferative effect of cetuximab by the MTT assay was not strong, and no correlation was observed between the antiproliferative effect of cetuximab and mutations in EGFR, KRAS, PIK3CA, BRAF and PTEN in these cell lines. Therefore, the mutation status of EGFR and downstream molecules were not useful for predicting the antitumor effects of cetuximab on HNSCC. Cetuximab-mediated ADCC was observed in these cell lines and might have been influenced by the expression of EGFR. Therefore, cetuximab-mediated ADCC seems to be an important part of the antitumor mechanisms of cetuximab and the expression levels of EGFR might influence the antitumor activity of cetuximab. Therefore, besides the antiproliferative effect of cetuximab by the MTT assay, it appeared important to evaluate cetuximabmediated ADCC as well as

Combined molecular targeted drug therapy for EGFR and HER-2 in head and neck squamous cell carcinoma cell lines

“…These IgG1 monoclonal antibodies induce ADCC by blocking the human Fc receptor, i.e., IgG1 antibody binds the Fc receptors expressed by NK cells, monocytes and granulocytes (17,34). Cetuximab-mediated ADCC has been reported in HNSCC (35-37); we have reported that cetuximab-induced ADCC and the antiproliferative effect by the MTT assay in HNSCC cells (24). However, trastuzumab-mediated ADCC in HNSCC has not been reported yet.…”

“…1-3). Previously we reported the expression levels of EGFR mRNA in HNSCC cell lines (24). All cell lines expressed mRNA for EGFR, HER-2 and HER-3; 12 cell lines expressed mRNA for HER-4; and 4 cell lines did not express mRNA for HER-4.…”

“…4). Further, the antiproliferative effect of trastuzumab alone were weaker than those of cetuximab evaluated by the same method and using the same cell lines (24). In this (C) YCU-T891 (EGFR low, HER-2 low).…”

“…As shown in Table I, combined cetuximab previously reported the expression levels of EGFR mRNA in the 16 HNSCC cell lines in a different study (24). To determine the correlation between the antiproliferative effect of combined cetuximab and trastuzumab treatment and the expression of EGFR, we analyzed the levels EGFR mRNA in 16 HNSCC cell lines (Figs.…”

HER family receptor and ligand status in thymic carcinoma

“…More precisely, in non-small cell lung cancer, only specific activating EGFR mutations are associated with response to targeted treatment with the TKI gefinitib or erlotinib [5]. Uncertainty still exists with regard to the relationship of EGFR expression and the clinical efficacy of cetuximab, a monoclonal EGFR antibody used in patients with head and neck squamous cell carcinoma [30]. Similarly, in colorectal cancer EGFR expression is not correlated with response to cetuximab.…”