[HTML][HTML] Response and acquired resistance to everolimus in anaplastic thyroid cancer

N Wagle, BC Grabiner, EM Van Allen… - … England Journal of …, 2014 - Mass Medical Soc
New England Journal of Medicine, 2014Mass Medical Soc
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 …
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.
The New England Journal Of Medicine