title: Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer models.
abstract: The dual PI3K-mTOR inhibitor BEZ235 was evaluated in preclinical models of nasopharyngeal carcinoma (NPC). The IC50 value of BEZ235 for growth was in the nanomolar range in vitro, induce G1 cycle arrest and apoptosis, and inhibited AKT and mTOR signaling in most NPC cell lines. No synergistic effect was observed when BEZ235 was combined with chemotherapy. BEZ235 increased MAPK activation in vitro but not in vivo. A daily schedule was more effective than a weekly schedule on tumor growth and inhibition of downstream mTOR signaling in vivo. The activity of BEZ235 maybe independent of the PIK3CA amplification and mutation status.
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: brigette@clo.cuhk.edu.hk.
authors.forename: Brigette B Y
authors.initials: BB
authors.lastname: Ma
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, USA.
authors.forename: Vivian W Y
authors.initials: VW
authors.lastname: Lui
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Connie W C
authors.initials: CW
authors.lastname: Hui
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Cecilia P Y
authors.initials: CP
authors.lastname: Lau
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Chi H
authors.initials: CH
authors.lastname: Wong
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Hui
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Margaret H L
authors.initials: MH
authors.lastname: Ng
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Suk H
authors.initials: SH
authors.lastname: Cheng
authors.affiliation: Department of Anatomy, University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Sai W
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: Department of Anatomy, University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Chi-Man
authors.initials: CM
authors.lastname: Tsang
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Crystal S F
authors.initials: CS
authors.lastname: Cheung
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Kakiu
authors.initials: K
authors.lastname: Ho
authors.affiliation: State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Cancer Drug Testing Unit, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D007093:Imidazoles; D017239:Paclitaxel; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011804:Quinolines; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C531198:dactolisib
keywords: BEZ235; MAPK activation; Nasopharyngeal carcinoma