Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer

Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer

Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here, we report that concomitant treatment of HNSCCs with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to rad...

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Bibliographic Details
Main Authors: Natalia Ricco, Amy Flor, Don Wolfgeher, Elena V. Efimova, Aishwarya Ramamurthy, Oliver K. Appelbe, Jacqueline Brinkman, Andrew W. Truman, Michael T. Spiotto, Stephen J. Kron
Format: Article
Language:English
Published: Wiley 2019-09-01
Series:Molecular Oncology
Subjects:
DNA damage response
HNSCC
mevalonate pathway
radiation sensitivity
senescence
statin
Online Access:https://doi.org/10.1002/1878-0261.12535
Description
Summary:Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here, we report that concomitant treatment of HNSCCs with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to radiosensitive HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin sensitized radioresistant SQ20B cells to ionizing radiation and reduced their clonogenic potential. Overall, this study reinforces the view that the mevalonate pathway is a promising therapeutic target in radioresistant HNSCCs.
ISSN:1574-7891
1878-0261

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