%0 Journal Article
%T HIF-1¦Á and mTOR ¨C Possible Novel Strategies of Targeted Therapies in p16-positive and -negative HNSCC
%A BENEDIKT KRAMER
%A CHRISTOPH ADERHOLD
%A MAX POLIT
%A NICOLE ROTTER
%A RICHARD BIRK
%J Archive of "Cancer Genomics & Proteomics".
%D 2018
%R 10.21873/cgp.20075
%X Background/Aim: Targeted therapy in head and neck squamous cell carcinoma (HNSCC) is limited. HIF-1¦Á and mTOR are involved in the formation of local tumor progression and distant metastasis. The present study analyzed the influence of well-established tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on the expression of HIF-1¦Á and mTOR in p16-positive and negative squamous cancer cells (SCC) in vitro in order to develop novel strategies in the treatment of HNSCC. Materials and Methods: Expression of HIF-1¦Á and mTOR was analyzed by using Sandwich-ELISA in p16-negative and p16-positive SCC after treatment with nilotinib, dasatinib, erlotinib and gefitinib (20 ¦Ìmol/l, 24-96 h of incubation). Results: All substances significantly reduced mTOR expression in both, p16-negative and p16-positive SCC (p<0.05). HIF-1¦Á expression was significantly reduced by all tested substances in p16-negative SCC. However, a statistically significant increase of HIF-1¦Á was observed in p16-positive SCC. Conclusion: This is the first study to investigate the alteration of expression levels of HIF-1¦Á and mTOR under selective tyrosine kinase inhibition in both p16-positive and -negative SCC. Our findings provide novel insights for a better understanding of HIF-1¦Á and mTOR in the tumor biology of HNSCC and their interaction with selective small-molecule inhibitors
%K mTOR
%K HIF-1¦Á
%K head and neck squamous cellcarcinoma
%K drug resistance
%K nilotinib
%K dasatinib
%K erlotinib
%K gefitinib
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971009/