Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer
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 extraordin...
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| Format: | Article |
| Language: | en_US |
| Published: |
New England Journal of Medicine
2017
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| Online Access: | http://hdl.handle.net/1721.1/108362 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1811092490419175424 |
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| author | 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. Kwiatkowski, David J. Jänne, Pasi A. Lorch, Jochen H. Wagle, Nikhil Grabiner, Brian Gray, Nathanael S Getz, Gad Asher Carter, Scott Sabatini, David Garraway, Levi A. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science 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. Kwiatkowski, David J. Jänne, Pasi A. Lorch, Jochen H. Wagle, Nikhil Grabiner, Brian Gray, Nathanael S Getz, Gad Asher Carter, Scott Sabatini, David Garraway, Levi A. |
| author_sort | Van Allen, Eliezer M. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:19:00Z |
| format | Article |
| id | mit-1721.1/108362 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:19:00Z |
| publishDate | 2017 |
| publisher | New England Journal of Medicine |
| record_format | dspace |
| spelling | mit-1721.1/1083622022-10-02T02:07:13Z Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer 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. Kwiatkowski, David J. Jänne, Pasi A. Lorch, Jochen H. Wagle, Nikhil Grabiner, Brian Gray, Nathanael S Getz, Gad Asher Carter, Scott Sabatini, David Garraway, Levi A. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Broad Institute of MIT and Harvard Massachusetts Institute of Technology. Department of Biology Wagle, Nikhil Grabiner, Brian Gray, Nathanael S Getz, Gad Asher Carter, Scott Sabatini, David Garraway, Levi 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. 2017-04-21T19:26:46Z 2017-04-21T19:26:46Z 2014-10 Article http://purl.org/eprint/type/JournalArticle 0028-4793 1533-4406 http://hdl.handle.net/1721.1/108362 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 https://orcid.org/0000-0002-1446-7256 en_US http://dx.doi.org/10.1056/NEJMoa1403352 New England Journal of Medicine 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. application/pdf New England Journal of Medicine New England Journal of Medicine |
| spellingShingle | 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. Kwiatkowski, David J. Jänne, Pasi A. Lorch, Jochen H. Wagle, Nikhil Grabiner, Brian Gray, Nathanael S Getz, Gad Asher Carter, Scott Sabatini, David Garraway, Levi A. Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer |
| title | Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer |
| title_full | Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer |
| title_fullStr | Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer |
| title_full_unstemmed | Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer |
| title_short | Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer |
| title_sort | response and acquired resistance to everolimus in anaplastic thyroid cancer |
| url | http://hdl.handle.net/1721.1/108362 https://orcid.org/0000-0002-1446-7256 |
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