Cetuximab-mediated ADCC activity is correlated with the cell surface expression level of EGFR but not with the KRAS/BRAF mutational status in colorectal cancer.

作者: YUKI SEO , YOSHIYUKI ISHII , HIROKI OCHIAI , KAZUMASA FUKUDA , SHINGO AKIMOTO

DOI: 10.3892/OR.2014.3077

关键词:

摘要: Cetuximab, an IgG1 monoclonal antibody against the epidermal growth factor receptor (EGFR), is widely used for treatment of metastatic colorectal cancer (mCRC). One mechanisms action considered to be antibody-dependent cell-mediated cytotoxicity (ADCC) triggered by Fcγ-R on natural killer cells. However, whether ADCC associated with EGFR expression and/or mutational status EGF downstream effectors (KRAS and BRAF) in (CRC) remains unclear. The aim present study was verify activities are cell surface levels KRAS BRAF. Five human CRC lines different BRAF statuses were selected evaluate activity using peripheral blood mononuclear cells (PBMCs) from healthy donors. Furthermore, tumor resected specimens patients level immunohistochemistry direct sequencing, while examined PBMCs same patients. A strong correlation observed between (correlation coefficient: 0.949; P=0.003). Of 13 specimens, a high significantly EGFR, when compared that low (P=0.027). In both patients, [standard partial regression coefficients: 0.911 (P=0.017) 0.660 (P=0.018), respectively], but not -0.101 (P=0.631) 0.160 (P=0.510), respectively]. Cetuximab-mediated may correlated regardless BRAF, CRC.

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