PUBLICATION

Malignant Peripheral Nerve Sheath Tumors

Authors
Durbin, A.D., Ki, D.H., He, S., Look, A.T.
ID
ZDB-PUB-160512-10
Date
2016
Source
Advances in experimental medicine and biology   916: 495-530 (Chapter)
Registered Authors
Durbin, Adam, He, Shuning, Ki, Dong Hyuk, Look, A. Thomas
Keywords
Akt, EGFR, MPNST, Malignant peripheral nerve sheath tumor, NF1, PI3K, RAS, Tumor modeling, Zebrafish, mTOR, p16INK4A, p53
MeSH Terms
  • Animals
  • Disease Models, Animal*
  • Mice
  • Nerve Sheath Neoplasms/genetics
  • Nerve Sheath Neoplasms/metabolism
  • Nerve Sheath Neoplasms/pathology*
  • Nerve Sheath Neoplasms/therapy
  • Rodentia
  • Zebrafish
PubMed
27165368 Full text @ Adv. Exp. Med. Biol.
Abstract
Malignant peripheral nerve sheath tumors (MPNST) are tumors derived from Schwann cells or Schwann cell precursors. Although rare overall, the incidence of MPNST has increased with improved clinical management of patients with the neurofibromatosis type 1 (NF1) tumor predisposition syndrome. Unfortunately, current treatment modalities for MPNST are limited, with no targeted therapies available and poor efficacy of conventional radiation and chemotherapeutic regimens. Many murine and zebrafish models of MPNST have been developed, which have helped to elucidate the genes and pathways that are dysregulated in MPNST tumorigenesis, including the p53, and the RB1, PI3K-Akt-mTOR, RAS-ERK and Wnt signaling pathways. Preclinical results have suggested that new therapies, including mTOR and ERK inhibitors, may synergize with conventional chemotherapy in human tumors. The discovery of new genome editing technologies, like CRISPR-cas9, and their successful application to the zebrafish model will enable rapid progress in the faithful modeling of MPNST molecular pathogenesis. The zebrafish model is especially suited for high throughput screening of new targeted therapeutics as well as drugs approved for other purposes, which may help to bring enhanced treatment modalities into human clinical trials for this devastating disease.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping