Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors
Abstract
The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is malignant peripheral nerve sheath tumor (MPNST). MPNSTs are aggressive Schwann cell-derived neoplasms that typically arise from precursor lesions such as plexiform neurofibromas. Although gross total resection of MPNSTs is potentially curative, this occurs in only a small minority of cases. Radiotherapy and chemotherapy may inhibit local recurrence but have almost no effect on patient mortality. NF1 patients have an approximate 10% lifetime risk of developing an MPNST and this risk increases to approximately 30% in patients with plexiform neurofibromas. Thus, development of safe and effective MPNST preventative therapies could have an important impact on NF1 patient morbidity and mortality. In this grant, we are testing the hypothesis that chronic administration of agents that promote apoptosis and/or inhibit pro-survival autophagy will inhibit MPNST formation and progression in transgenic mouse models of MPNST. Specifically, we are examining the mechanisms of action and in vivo utility of two classes of drugs, BH3 mimetics and lysosomotropic agents, on MPNSTs. The drugs that we are testing are approved for human use and could be rapidly advanced into human MPNST clinical trials if our pre-clinical testing yields positive results.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2015
- Accession Number
- ADA620350
Entities
People
- Kevin A. Roth
Organizations
- University of Alabama