Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines

• Verfasst von: Affolter, Annette [VerfasserIn]
• Verfasst von: Jensen, Alexandra [VerfasserIn]
• Titel: Multikinase inhibitors sorafenib and sunitinib as radiosensitizers in head and neck cancer cell lines
• Verf.angabe: Annette Affolter, MD, Gerson Samosny, MD, Anne-Sophie Heimes, MD, Johanna Schneider, MD, Wilko Weichert, MD, Albrecht Stenzinger, MD, Katharina Sommer, Alexandra Jensen, MD, Arnulf Mayer, MD, Walburgis Brenner, PhD, Wolf J. Mann, MD, Jürgen Brieger, PhD
• E-Jahr: 2017
• Jahr: 21 February 2017
• Umfang: 10 S.
• Fussnoten: Gesehen am 13.12.2018
• Titel Quelle: Enthalten in: Head & neck
• Ort Quelle: New York, NY [u.a.] : Wiley Interscience, 1979
• Jahr Quelle: 2017
• Band/Heft Quelle: 39(2017), 4, Seite 623-632
• ISSN Quelle: 1097-0347
• DOI: doi:10.1002/hed.24557
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: head and neck cancer
• Sach-SW: human head and neck squamous cell carcinoma (HNSCC)
• Sach-SW: mitogen‐activated protein kinase (MAPK) signaling pathway
• Sach-SW: multikinase inhibitor
• Sach-SW: radioresistance
• Sach-SW: tissue microarray
• K10plus-PPN: 1572165103

Abstract

Abstract 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