Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer
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Sabatini_Response and.pdf
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Author(s)
Van Allen, Eliezer M.
Amin-Mansour, Ali
Taylor-Weiner, Amaro
Rosenberg, Mara
Barletta, Justine A.
Guo, Yanan
Swanson, Scott J.
Ruan, Daniel T.
Hanna, Glenn J.
Haddad, Robert I.
Date Issued
October 2014
Journal
New England Journal of Medicine
Publisher
New England Journal of Medicine
Citation
Wagle, Nikhil; Grabiner, Brian C.; Van Allen, Eliezer M.; Amin-Mansour, Ali; Taylor-Weiner, Amaro; Rosenberg, Mara; Gray, Nathanael et al. “Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer.” New England Journal of Medicine 371, no. 15 (October 2014): 1426–1433. © New England Journal of Medicine
Version
Final published version
Abstract
Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed a nonsense mutation in TSC2, a negative regulator of mTOR, suggesting a mechanism for exquisite sensitivity to everolimus. The resistant tumor also harbored a mutation in MTOR that confers resistance to allosteric mTOR inhibition. The mutation remains sensitive to mTOR kinase inhibitors.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1056/NEJMoa1403352
