Response and acquired resistance to everolimus in anaplastic thyroid cancer.
N Engl J Med
; 371(15): 1426-33, 2014 Oct 09.
Article
em En
| MEDLINE
| ID: mdl-25295501
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Glândula Tireoide
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Resistencia a Medicamentos Antineoplásicos
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Sirolimo
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Proteínas Supressoras de Tumor
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Serina-Treonina Quinases TOR
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
Limite:
Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article