Bosutinib Inhibits EGFR Activation in Head and Neck Cancer

• Published in: International journal of molecular sciences Vol. 19; no. 7; p. 1824
• Main Authors: Segrelles, Carmen, Contreras, David, Navarro, Elena M, Gutiérrez-Muñoz, Carmen, García-Escudero, Ramón, Paramio, Jesús M, Lorz, Corina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.06.2018; MDPI
• Subjects: Activation; Alpelisib; Aniline Compounds - pharmacology; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Biotechnology; Bosutinib; cancer cell lines; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Chronic myeloid leukemia; Class I Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Class I Phosphatidylinositol 3-Kinases - genetics; Class I Phosphatidylinositol 3-Kinases - metabolism; Data processing; Drug Combinations; Drug screening; Drug Synergism; EGFR inhibitors; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Gene Expression Regulation, Neoplastic; Growth factors; Head & neck cancer; head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - enzymology; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Humans; Inhibitors; Injections, Subcutaneous; Mice; Mice, Nude; Mutation; Myeloid leukemia; Nitriles - pharmacology; Patients; Phosphorylation; Proto-Oncogene Proteins c-abl - antagonists & inhibitors; Proto-Oncogene Proteins c-abl - genetics; Proto-Oncogene Proteins c-abl - metabolism; Quinolines - pharmacology; Signal Transduction; Squamous cell carcinoma; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - genetics; src-Family Kinases - metabolism; Synergistic effect; Targeted cancer therapy; targeted therapies; Thiazoles - pharmacology; Tumor Burden - drug effects; Tumors; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; Alpelisib; EGFR inhibitors; cancer cell lines; head and neck cancer; targeted therapies; Bosutinib
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19071824

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 , the combination of Bosutinib with the PI3Kα inhibitor Alpelisib showed a synergistic effect. These results suggest that Bosutinib could be a new effective drug for the treatment of HNSCC, particularly in tumors with high EGFR activity. Its combination with Alpelisib could especially benefit patients bearing activating mutations of .