Malignant peripheral nerve sheath tumour (MPNST): the clinical implications of cellular signalling pathways

Expert Rev Mol Med. 2009 Oct 19;11:e30. doi: 10.1017/S1462399409001227.

Abstract

Malignant peripheral nerve sheath tumour (MPNST) is a rare malignancy accounting for 3-10% of all soft tissue sarcomas. Most MPNSTs arise in association with peripheral nerves or deep neurofibromas and may originate from neural crest cells, although the specific cell of origin is uncertain. Approximately half of MPNSTs occur in the setting of neurofibromatosis type 1 (NF1), an autosomal dominant disorder with an incidence of approximately one in 3500 persons; the remainder of MPNSTs develop sporadically. In addition to a variety of clinical manifestations, approximately 8-13% of NF1 patients develop MPNSTs, which are the leading cause of NF1-related mortality. Surgical resection is the mainstay of MPNST clinical management. However, because of invasive growth, propensity to metastasise, and limited sensitivity to chemotherapy and radiation, MPNST has a guarded to poor prognosis. Five-year survival rates of only 20-50% indicate an urgent need for improved therapeutic approaches. Recent work in this field has identified several altered intracellular signal transduction cascades and deregulated tyrosine kinase receptors, posing the possibility of personalised, targeted therapeutics. However, expanded knowledge of MPNST molecular pathobiology will be needed to meaningfully apply such approaches for the benefit of afflicted patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ErbB Receptors / metabolism
  • Humans
  • Nerve Sheath Neoplasms / diagnosis*
  • Nerve Sheath Neoplasms / metabolism*
  • Nerve Sheath Neoplasms / therapy
  • Neurofibromin 1 / metabolism*
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases

Substances

  • Neurofibromin 1
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • EGFR protein, human
  • ErbB Receptors
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Proto-Oncogene Proteins p21(ras)