Dual Pi3k/Mtor Blockade By Nvp-Bez235 Sensitizes Head And Neck Squamous Cell Carcinoma To Radiotherapy

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide accounting for over 500,000 new cases annually. Chemoradiotherapy is a mainstay of treatment. However, long-term survival rate has only improved marginally; and the severe toxicity often associated with chemoradiotherapy advocates a need for better radiosensitization strategies. Akt/mTOR pathway is frequently activated in HNSCC cells. This study sought to explore whether NVP-BEZ235, a novel imidazo [4,5-c] quinoline derivative that inhibits PI3K and mTOR kinase activity, has radiosensitization effect in the treatment of HNSCC. MTT assays revealed that NVP-BEZ235 dose-dependently inhibited the growth of two HNSCC cell lines, SAS and OC3 at low nanomolar concentrations; IC50 values were 27.87 nmol/L in SAS cells and 42.63 nmol/L in OC3 cells. By using clonogenic assay and median effect analysis, we found that dual PI3K/mTOR inhibition effectively sensitized SAS and OC3 cell lines to radiation with CI (combination index) value Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4594. doi:1538-7445.AM2012-4594