Open AccessMevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
Author(s) -
Ricco Natalia,
Flor Amy,
Wolfgeher Don,
Efimova Elena V.,
Ramamurthy Aishwarya,
Appelbe Oliver K.,
Brinkman Jacqueline,
Truman Andrew W.,
Spiotto Michael T.,
Kron Stephen J.
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12535
Subject(s) - radioresistance , mevalonate pathway , head and neck squamous cell carcinoma , cancer research , head and neck cancer , clonogenic assay , radiation therapy , medicine , concomitant , radiosensitivity , biology , cell , enzyme , biochemistry , biosynthesis
Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma ( HNSCC ). Here, we report that concomitant treatment of HNSCC s with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to radiosensitive HNSCC s revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin sensitized radioresistant SQ 20B 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 HNSCC s.