Inhibition of mTORC1 signaling reduces tumor growth but does not prevent cancer progression in a mouse model of thyroid cancer

GUIGON CELINE; FOZZATTI LAURA; LU CHANGXUE; WILLINGHAM MARK; CHENG SHEUE-YANN

OXFORD UNIV PRESS

Año: 2010 vol. 31 p. 1284 - 1284

Selective drugs targeting dysregulated oncogenic pathways arepromising cancer therapies. Because the mammalian target ofrapamycin complex 1 (mTORC1) pathway is hyperactivated inhuman follicular thyroid cancer (FTC), we hypothesized that itsinhibition could block cancer development and progression. We,therefore, analyzed the effect of a treatment with a specificmTORC1 inhibitor (RAD001) in a faithful mouse model of FTCwith constitutive mTORC1 activation (TRbPV/PVPten1/2 mice).The treatment did not prevent capsular and vascular invasionof the thyroid and the occurrence of lung metastasis. However,it substantially decelerated thyroid tumor growth, therebyprolonging TRbPV/PVPten1/2 mouse life span. RAD001 efficientlyinhibited mTORC1 activity, as shown by the reduced phosphorylationof its downstream targets involved in the activity of thetranslation machinery, such as ribosomal S6 kinase (p70S6K),e