| First Author | Giovannini M | Year | 2014 |
| Journal | Neuro Oncol | Volume | 16 |
| Issue | 4 | Pages | 493-504 |
| PubMed ID | 24414536 | Mgi Jnum | J:261548 |
| Mgi Id | MGI:6156733 | Doi | 10.1093/neuonc/not242 |
| Citation | Giovannini M, et al. (2014) mTORC1 inhibition delays growth of neurofibromatosis type 2 schwannoma. Neuro Oncol 16(4):493-504 |
| abstractText | 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 that treatment with the mTORC1 inhibitor rapamycin reduced the severity of NF2-related Schwann cell tumorigenesis without significant toxicity. Consistent with these results, in an NF2 patient with growing vestibular schwannomas, the rapalog sirolimus induced tumor growth arrest. CONCLUSIONS: Taken together, these results constitute definitive evidence that justifies proceeding with clinical trials using mTORC1-targeted agents in selected patients with NF2 and in patients with NF2-related sporadic tumors. |
