Recent advances of targeted therapy for tumors associated with neurofibromatosis type I

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome occurring predominantly in children.Neurofibromin encoded by NF1 gene is a kind of Ras-GTPase capable of transforming active Ras-GTP into inactive Ras-GDP.Thus neurofibromin can decrease the downstream Ras signaling.NF1 patients have two major Ras downstream pathways of abnormal high level activity, namely Raf-MEK-ERK and PI3K-AKT-mTOR.The inhibitors of MEK and mTOR have proved effective in reducing tumor volume and prolonging time to progress.In addition, c-kit signaling in microenvironment is essential for tumor progression.As a kind of inhibitor of c-kit, Imatinib is the first drug of targeted therapy proved clinically effective in NF1 tumor.This review will highlight the advances on preclinical researches and clinical trials of targeted therapy for NF1 associated tumors, including plexiform neurofibromas (PNTs), malignant peripheral nerve sheath tumors (MPNSTs) and optic pathway glioma. Key words: Neurofibromatosis 1; Molecular target therapy; Neurofibroma, plexiform; Glioma Neurilemmoma