Response and acquired resistance to everolimus in anaplastic thyroid cancer.

N Engl J Med
Authors
Keywords
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
Journal
N Engl J Med
Volume
371
Issue
15
Pages
1426-33
Date Published
2014 Oct 09
ISSN
1533-4406
URL
DOI
10.1056/NEJMoa1403352
PubMed ID
25295501
PubMed Central ID
PMC4564868
Links
Grant list
R33 CA155554 / CA / NCI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
Howard Hughes Medical Institute / United States