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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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717759/
https://www.ncbi.nlm.nih.gov/pubmed/31225926
http://dx.doi.org/10.1002/1878-0261.12535
Descripción
Sumario: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.

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