Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer
Menée sur une patiente atteinte d'un carcinome anaplasique de la thyroïde, cette étude identifie une mutation du gène TSC2 associée à une réponse thérapeutique exceptionnelle à l'everolimus
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.