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Response and acquired resistance to everolimus in anaplastic thyroid cancer. | LitMetric

Response and acquired resistance to everolimus in anaplastic thyroid cancer.

N Engl J Med

From the Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School (N.W., E.M.V.A., N.G., R.I.H., D.J.K., P.A.J., L.A.G., J.H.L.), the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (N.W., E.M.V.A., Y.G., R.I.H., D.J.K., P.A.J., L.A.G., J.H.L.), the Departments of Pathology (J.A.B.) and Surgery (S.J.S., D.T.R.), Brigham and Women's Hospital, the Department of Medicine, Beth Israel Deaconess Medical Center (G.J.H.), and Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute (P.A.J.) - all in Boston; and Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard (N.W., E.M.V.A., A.A.-M., A.T.-W., M.R., G.G., D.J.K., S.L.C., D.M.S., L.A.G.), Whitehead Institute for Biomedical Research and the MIT Department of Biology (B.C.G., D.M.S.), and Howard Hughes Medical Institute, MIT (B.C.G., D.M.S.) - all in Cambridge, MA.

Published: October 2014

AI Article Synopsis

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564868PMC
http://dx.doi.org/10.1056/NEJMoa1403352DOI Listing

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