title: In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer.
abstract: OBJECTIVE
  The purpose of the present study was to explore the antiproliferative effect of BYL719, a specific inhibitor for phosphatidylinositol 3-kinase (PI3K) p110α, in human head and neck cancer cell lines, as a single agent or in combination with the irreversible EGFR tyrosine kinase inhibitor, dacomitinib.
  
  
  METHODS
  Six head and neck cancer cell lines consisting of two PIK3CA mutant cell lines, SNU-1076 and Detroit562, and four PIK3CA wild-type cell lines, SNU-1066, SNU-1041, FaDu and SCC25, were analyzed.
  
  
  RESULTS
  The PIK3CA-mutant cell lines were more sensitive to BYL719 than the PIK3CA wild-type cell lines. Following BYL719 treatment, all PIK3CA wild-type cell lines, except for the SNU-1066 cell line, exhibited higher IC50 values compared to the PIK3CA mutant cell lines. Administration of BYL719 induced cell cycle G0/G1 arrest and resulted in increased apoptosis in a dose-dependant manner. Furthermore, the administration of BYL719 reduced the level of p-mTOR, p-AKT and p-S6 expression indicating the down-regulation of downstream signaling.
  
  
  CONCLUSIONS
  BYL719, a PI3K alpha selective blocker, could be a promising factor in the treatment of head and neck cancer either as a single agent or in combination with dacomitinib.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong-Oon
authors.initials: YO
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea heo1013@snu.ac.kr.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006258:Head and Neck Neoplasms; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D052999:Quinazolinones / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D052999:Quinazolinones; D013844:Thiazoles; C585539:Alpelisib; C525726:dacomitinib
keywords: BYL719; Head and neck squamous cell carcinoma; PIK3CA; dacomitinib