Abstrakt

Erlotinib (Tarceva®) inhibits oral cavity carcinoma and synergizes with cisplatin and ionizing radiation in vitro

Ray Hinerman, Weiyi Gao, Hassan H Ramadan, Cynthia Cunningham and Peilin Zhang

Epidermal growth factor (EGF) plays important roles in the growth and development of normal epidermis and numerous malignant human tumors. EGF is a secreted protein and binds to a heterodimeric receptor which possesses an intrinsic tyrosine kinase activity. EGF receptor (EGFR) kinase inhibitor has been shown to specifically inhibit the tumor growth of lung cancer, head and neck cancer, colon cancer and others. The cytotoxic effect of the newly developed tyrosine kinase inhibitor erlotinib or OSI-774 (Tarceva^®, OSI Pharmaceuticals) on the oral cavity cancer in cell culture condition was investigated. Tarceva showed a dose-dependent inhibition of the growth of squamous carcinoma of the tongue (SCC-015) in cytotoxic assays. The inhibition of the SCC-015 cells by Tarceva appeared to be within the physiologically achievable concentrations (low μm concentrations). The effect of Tarceva on SCC-15 cells appears to be intra-S phase inhibition as well as an inhibition of G2/M transition of the cell cycle by flow cytometry study. Furthermore, Tarceva can synergistically inhibit the SCC-15 cell growth with cisplatin and radiation. It has also been shown by this group that approximately 56% of the head and neck squamous cell carcinoma tumor specimens express EGFR by tissue microarray study in combination with immunohistochemical staining and automated imaging analyses. These results represent promising preliminary data for further clinical trials of this kind of drug as adjuvant therapy for squamous carcinoma of the oral cavity.