Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer
Author
Ricco Pacheco, Natalia
Flor, Amy
Wolfgeher, Donald
Efimova, Elena V.
Ramamurthy, Aishwarya
Appelbe, Oliver K.
Brinkman, Jacqueline
Truman, Andrew W.
Spiotto, Michael T.
Kron, Stephen J.
Publication date
2019-06-21ISSN
1878-0261
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.
Document Type
Article
Document version
Accepted version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
ADN--Anàlisi
Radiació
Estatines (Medicaments cardiovasculars)
Radioteràpia
ADN--Análisis
Radiación
Estatinas
Radioterapia
DNA--Analysis
Radiation
Statins (Cardiovascular agents)
Radiotherapy
Pages
17
Publisher
Wiley
Collection
13; 9
Is part of
Molecular Oncology
Citation
Ricco, Natalia; Flor, Amy; Wolfgeher, Don [et al.]. Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer. Molecular Oncology, vol. 13, núm. 9, p. 1927-1943. Disponible en: <https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1878-0261.12535>. Fecha de acceso: 4 ene. 2020. DOI: 10.1002/1878-0261.12535
This item appears in the following Collection(s)
- Ciències de la Salut [740]
Rights
© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. 1927. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/