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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1927-1943
Number of pages17
JournalMolecular oncology
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2019
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

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