| Literature DB >> 25295501 |
Nikhil Wagle1, Brian C Grabiner, Eliezer M Van Allen, Ali Amin-Mansour, Amaro Taylor-Weiner, Mara Rosenberg, Nathanael Gray, Justine A Barletta, Yanan Guo, Scott J 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.
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.Entities:
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Year: 2014 PMID： 25295501 PMCID： PMC4564868 DOI： 10.1056/NEJMoa1403352
Source DB: PubMed Journal: N Engl J Med ISSN： 0028-4793 Impact factor: 91.245