Abstract 5522: Anticancer activity of novel PI3K inhibitor BYL719 in head and neck cancer cell lines

Abstract

Abstract Introduction: Activating mutations of the PIK3CA gene occur frequently in head and neck squamous cell carcinoma. The purpose of this study was to explore the antiproliferative effect of BYL719, specific inhibitor for phosphatidylinositol 3-kinase (PI3K) p110α, in human head and neck cancer cell lines as a single agent or in combination with irreversible EGFR TKI. Methods: Six head and neck cancer cell lines (SNU-1066, SNU-1041, SNU-1076, SCC25, Detroit562, and FaDu) were tested. The growth inhibitory effect was assessed using the modified tetrazolium bromide assay. The cell cycle at various concentrations of BYL719 was analyzed by flow cytometry, and analysis of downstream molecules was performed by western blot analysis. Mutational profiles of cell lines were screened by Cancer Cell Line Encyclopedia. Results: PIK3CA mutant cell lines (SNU-1076 and Detroit562) were more sensitive to BYL719 than PIK3CA wild type cell lines (SNU-1066, SNU-1041, SCC25, and FaDu). PIK3CA wild type cell lines except SNU-1066 exhibited higher IC50 values for BYL719 (IC50 were 6.82, 1.10 μM in mutant cell lines and 1.13, 20.65, 19.67, 49.30 μM in wild type cell lines, respectively). BYL719 induced G0/1 arrest and resulted in apoptosis with dose dependant manner, in PIK3CA mutant cell lines. It reduced the level of p-mTOR, p-AKT, p-S6, suggesting its effectiveness in inhibition of translation and protein synthesis. BYL719 combined with dacomitinib also showed a synergistic inhibitory effect on PIK3CA mutant cell lines, while PIK3CA wild type cell lines showed no synergism. Conclusion: BYL719 could be a promising treatment for head and neck cancer cells with PIK3CA mutation as a single agent or in combination with dacomitinib. The beneficial effects of BYL719 in in vitro studies for head and neck cancer warrant a further clinical investigation. Citation Format: Bhumsuk Keam, Yong-Oon Ahn, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Dae Seog Heo. Anticancer activity of novel PI3K inhibitor BYL719 in head and neck cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5522. doi:10.1158/1538-7445.AM2014-5522