Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer | Zendy

Nikhil Wagle | Zendy; Brian C. Grabiner | Zendy; Eliezer M. Van Allen | Zendy; Ali AminMansour | Zendy; Amaro TaylorWeiner | Zendy; Mara Rosenberg | Zendy; Nathanael S. Gray | Zendy; Justine A. Barletta | Zendy; Junming Guo | Zendy; Steven Swanson | Zendy; Daniel T. Ruan | Zendy; Glenn J. Hanna | Zendy; Robert I. Haddad | Zendy; Gad Getz | Zendy; David J. Kwiatkowski | Zendy; Scott L. Carter | Zendy; David M. Sabatini | Zendy; Pasi A. Jänne | Zendy; Levi A. Garraway | Zendy; Jochen H. Lorch | Zendy

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Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer

Author(s) -

Nikhil Wagle,

Brian C. Grabiner,

Eliezer M. Van Allen,

Ali AminMansour,

Amaro TaylorWeiner,

Mara Rosenberg,

Nathanael S. Gray,

Justine A. Barletta,

Junming Guo,

Steven Swanson,

Daniel T. Ruan,

Glenn J. Hanna,

Robert I. Haddad,

Gad Getz,

David J. Kwiatkowski,

Scott L. Carter,

David M. Sabatini,

Pasi A. Jänne,

Levi A. Garraway,

Jochen H. Lorch

Publication year - 2014

Publication title -

new england journal of medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 19.889

H-Index - 1030

eISSN - 1533-4406

pISSN - 0028-4793

DOI - 10.1056/nejmoa1403352

Subject(s) - everolimus , pi3k/akt/mtor pathway , medicine , cancer research , rptor , drug resistance , discovery and development of mtor inhibitors , sirolimus , mutation , regulator , oncology , biology , signal transduction , genetics , gene

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.

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