Response and acquired resistance to everolimus in anaplastic thyroid cancer.
case_report · Level V
Where this comes from
- Record sourced from PubMed, PMID 25295501.
- Also identified by DOI 10.1056/NEJMoa1403352 and PMC identifier 4564868.
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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.
Medical subject headings
- Antineoplastic Agents
- Drug Resistance, Neoplasm
- Sirolimus
- TOR Serine-Threonine Kinases
- Thyroid Neoplasms
- Tumor Suppressor Proteins