Study on a new combination chemotherapy for head and neck squamous cell carcinomas

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BRAK/CXCL14 is a chemokine that is expressed in normal tissues, and is important for maintaining homeostasis. BRAK has many functions such as inhibition of angiogenesis and chemotaxis of monocytes as well as macrophaghes. BRAK is absent from or expressed at very low levels in head and neck squamous cell carcinoma(HNSCC), and this is closely correlated with tumorigenesis and progression of HNSCC. Forced expression of BRAK chemokine by the gene transfection into HNSCC or BRAK transgenic mice reduced the tumorigenicity of the cells in xenografts, and BRAK was considered to be a target molecule for the cancer treatment. In the present study, we elucidated that low expression of BRAK in HNSCC was due to mutation of BRAK promotor region by methylation. The low expression level of BRAK in HNSCC is restored by treatment of the cells with anti-methylation drug. HNSCC overexpressed BRAK by EGF receptor antagonist(gefitinib) and anti-methylation drug gave rise to susceptible to tumor regression. The anti-tumor effect using gefitinib and anti-cancer drugs is thus feasible for combination chemotherapy in HNSCC.