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Journal Article
Review
The promise of signal transduction in genetically driven sarcomas of the nerve.
Experimental Neurology 2018 January
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome. Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas arising from peripheral nerve sheaths, and the most commonly lethal feature associated with NF1. The hallmark of NF1 and NF1-related MPNST is the loss of neurofibromin expression. Loss of neurofibromin is considered a tumor-promoting event, and leads to constitutive activation of RAS and its downstream effectors. However, RAS activation alone is not sufficient for MPNST formation, and additional tumor suppressors and signaling pathways have been implicated in tumorigenesis of MPNST. Taking advantage of the rapid development of novel therapeutics targeting key molecular pathways across all cancer types, the best-in-class modulators of these pathways can be assessed in pre-clinical models and translated into clinical trials for patients with MPNST. Here, we describe the genetic changes and molecular pathways that drive MPNST formation and highlight the promise of signal transduction to identify therapies that may treat these tumors more effectively.
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