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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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
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author 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.
author_facet 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.
author_sort Ricco, Natalia
collection PubMed
description 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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spelling pubmed-67177592019-09-06 Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer 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. Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2019-07-26 2019-09 /pmc/articles/PMC6717759/ /pubmed/31225926 http://dx.doi.org/10.1002/1878-0261.12535 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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.
Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
title Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
title_full Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
title_fullStr Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
title_full_unstemmed Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
title_short Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
title_sort mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
topic Research Articles
url 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
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