Response and acquired resistance to everolimus in anaplastic thyroid cancer.
N Engl J Med
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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. |
Year of Publication | 2014
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Journal | N Engl J Med
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Volume | 371
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Issue | 15
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Pages | 1426-33
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Date Published | 2014 Oct 09
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ISSN | 1533-4406
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URL | |
DOI | 10.1056/NEJMoa1403352
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PubMed ID | 25295501
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PubMed Central ID | PMC4564868
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Grant list | R33 CA155554 / CA / NCI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
Howard Hughes Medical Institute / United States
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