HIF-1α and mTOR - Possible Novel Strategies of Targeted Therapies in p16-positive and -negative HNSCC.

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HIF-1α and mTOR - Possible Novel Strategies of Targeted Therapies in p16-positive and -negative HNSCC.

Cancer Genomics Proteomics. 2018 May-Jun;15(3):175-184

Authors: Kramer B, Polit M, Birk R, Rotter N, Aderhold C

Abstract
BACKGROUND/AIM: Targeted therapy in head and neck squamous cell carcinoma (HNSCC) is limited. HIF-1α 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-1α 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-1α and mTOR was analyzed by using Sandwich-ELISA in p16-negative and p16-positive SCC after treatment with nilotinib, dasatinib, erlotinib and gefitinib (20 μmol/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-1α expression was significantly reduced by all tested substances in p16-negative SCC. However, a statistically significant increase of HIF-1α was observed in p16-positive SCC.
CONCLUSION: This is the first study to investigate the alteration of expression levels of HIF-1α 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-1α and mTOR in the tumor biology of HNSCC and their interaction with selective small-molecule inhibitors.

PMID: 29695399 [PubMed - in process]

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