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Targeting irradiation-induced mitogen-activated protein kinase activation in vitro and in an ex vivo model for human head and neck cancer

Background Despite new radiotherapeutic strategies, radioresistance in head and neck squamous cell carcinoma (HNSCC) remains a major problem. Preclinical model systems are needed to identify resistance mechanisms in this heterogeneous entity. Methods We elucidated the interplay among mitogen-activat...

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Main Authors: Affolter, Annette (Author) , Muller, Marie France (Author) , Sommer, Katharina Sophia (Author) , Stenzinger, Albrecht (Author) , Plath, Karim (Author) , Lorenz, Katja (Author) , Wolf, Thomas (Author) , Sharma, Sarika (Author) , Wolf, Janina Luisa (Author) , Weber, Klaus-Josef (Author) , Freier, Kolja (Author) , Plinkert, Peter K. (Author) , Heß, Jochen (Author) , Weichert, Wilko (Author)
Format: Article (Journal)
Language:English
Published: 26 February 2016
In: Head & neck
Year: 2016, Volume: 38, Issue: S1, Pages: E2049-E2061
ISSN:1097-0347
DOI:10.1002/hed.24376
Online Access:Verlag, Volltext: https://doi.org/10.1002/hed.24376
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/hed.24376
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Author Notes:Annette Affolter, MD, Marie-France Muller, Katharina Sommer, Albrecht Stenzinger, MD, Karim Zaoui, MD, Katja Lorenz, Thomas Wolf, PhD, Sarika Sharma, PhD, Janina Wolf, Sven Perner, Klaus-Josef Weber, PhD, Kolja Freier, MD, Peter K. Plinkert, MD, Jochen Hess, PhD, Wilko Weichert, MD
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Summary:Background Despite new radiotherapeutic strategies, radioresistance in head and neck squamous cell carcinoma (HNSCC) remains a major problem. Preclinical model systems are needed to identify resistance mechanisms in this heterogeneous entity. Methods We elucidated the interplay among mitogen-activated protein kinase (MAPK)-inhibition, radiation, and p53 mutations in vitro and in a novel ex vivo model derived from vital human HNSCC samples. HNSCC cell lines (p53WT/mut) were treated with the mitogen-activated protein kinase (MEK)-inhibitor PD-0325901 and subsequently irradiated. Radiosensitization was functionally assessed and evaluated in the ex vivo model. Results We observed a pronounced irradiation-induced extracellular signal-regulated kinase (ERK) phosphorylation in 2 cell lines, which was independent of their p53 mutation status and associated with PD-0325901-related radiosensitization in a clonogenic assay. Heterogeneity in irradiation-induced ERK phosphorylation and in radiosensitization after MEK-inhibition was also reflected in the ex vivo model. Conclusion We provide experimental evidence for radiosensitizing effects of PD-0325901 in HNSCC. The ex vivo culture technology might offer a promising tool for individualized drug efficacy testing. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2049-E2061, 2016
Item Description:Gesehen am 22.11.2019
Physical Description:Online Resource
ISSN:1097-0347
DOI:10.1002/hed.24376

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