byl719 and bosutinib

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and although new therapeutic approaches have been recently evaluated, overall patient survival is still poor. Thus, new effective and selective clinical treatments are urgently needed. An analysis of data from large-scale, high-throughput drug screening cell line projects identified Bosutinib, a Src/Abl inhibitor that is currently used for the treatment of chronic myelogenous leukemia, as a candidate drug to treat HNSCC. Using a panel of HNSCC-derived cell lines, we found that treatment with Bosutinib reduced cell proliferation and induced apoptosis of sensitive cell lines. The drug rapidly inhibited Src and EGFR (epidermal growth factor receptor) phosphorylation, and sensitivity to Bosutinib was correlated with the activation status of EGFR. Similar findings were observed in in vivo xenograft assays using HNSCC derived cells. Moreover, in the presence of mutations in

Topics: Aniline Compounds; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Class I Phosphatidylinositol 3-Kinases; Drug Combinations; Drug Synergism; ErbB Receptors; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Injections, Subcutaneous; Mice; Mice, Nude; Nitriles; Proto-Oncogene Proteins c-abl; Quinolines; Signal Transduction; src-Family Kinases; Thiazoles; Tumor Burden; Xenograft Model Antitumor Assays