MTORC1 inhibition delays growth of neurofibromatosis type 2 schwannoma.

ABSTRACT:

Background

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant genetic disorder, resulting in a variety of neural tumors, with bilateral vestibular schwannomas as the most frequent manifestation. Recently, merlin, the NF2 tumor suppressor, has been identified as a novel negative regulator of mammalian target of rapamycin complex 1 (mTORC1); functional loss of merlin was shown to result in elevated mTORC1 signaling in NF2-related tumors. Thus, mTORC1 pathway inhibition may be a useful targeted therapeutic approach.

Methods

We studied in vitro cell models, cohorts of mice allografted with Nf2(-/-) Schwann cells, and a genetically modified mouse model of NF2 schwannoma in order to evaluate the efficacy of the proposed targeted therapy for NF2.

Results

We found th

SUBMITTER: Giovannini M 

PROVIDER: S-EPMC3956353 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature