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Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines
Author(s) -
Affolter Annette,
Samosny Gerson,
Heimes AnneSophie,
Schneider Johanna,
Weichert Wilko,
Stenzinger Albrecht,
Sommer Katharina,
Jensen Alexandra,
Mayer Arnulf,
Brenner Walburgis,
Mann Wolf J.,
Brieger Jürgen
Publication year - 2017
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.24557
Subject(s) - sorafenib , sunitinib , cancer research , head and neck squamous cell carcinoma , clonogenic assay , mapk/erk pathway , medicine , radioresistance , radiosensitizer , kinase , apoptosis , cancer , head and neck cancer , radiation therapy , chemistry , biology , hepatocellular carcinoma , microbiology and biotechnology , biochemistry
Background Radioresistance is a common feature of head and neck squamous cell carcinoma (HNSCC). We previously showed that the irradiation‐ activated vascular endothelial growth factor (VEGF)‐extracellular signal‐regulated kinase (ERK)‐axis is fundamental for the survival of resistant tumors. In this study, we examined if treatment with potent multikinase (MK) inhibitors, sorafenib and sunitinib, could radiosensitize tumor cells. Methods Cultured HNSCC cell lines were treated with inhibitors and subsequently irradiated. Radiosensitizing effects were functionally assessed by annexin‐V apoptosis and clonogenic assays and confirmed by Western blot. Additionally, we surveyed human HNSCC tissue microarrays (TMAs) for activated ERK expression. Results Based on combination indexes, we found that combining irradiation with both inhibitors exerted strong and supra‐additive antitumor effects on clonogenic survival. Kinase inhibition enhanced irradiation‐induced apoptotic rates and inhibited postradiogenic phospho‐ERK‐expression. Patients with recurrent HNSCC displayed significantly lower extracellular signal‐regulated kinase phosphorylation (pERK) levels than relapse‐free patients. Conclusion We propose further evaluation of sorafenib and sunitinib as potential radiosensitizing agents in HNSCC treatment. © 2017 Wiley Periodicals, Inc. Head Neck 39: 623–632, 2017