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Mol Oncol. 2019 Sep;13(9):1927-1943. doi: 10.1002/1878-0261.12535. Epub 2019 Jul 26.

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

Author information

1
Department of Molecular Genetics and Cell Biology, The University of Chicago, IL, USA.
2
Department of Biological Sciences, University of North Carolina at Charlotte, NC, USA.
3
Department of Radiation and Cellular Oncology, University of Chicago Medical Center, IL, USA.
4
Department of Radiation Oncology, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA.

Abstract

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.

KEYWORDS:

HNSCC ; DNA damage response; mevalonate pathway; radiation sensitivity; senescence; statin

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