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

Published online by Cambridge University Press:  19 October 2009

Daniela Katz ,
Alexander Lazar  and
Dina Lev
Daniela Katz
Affiliation:
Department of Surgical Oncology and Sarcoma Research Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Alexander Lazar
Affiliation:
Department of Pathology and Sarcoma Research Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Dina Lev*
Affiliation:
Department of Cancer Biology and Sarcoma Research Center, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
*
*Corresponding author: Dina Lev, Department of Cancer Biology and Sarcoma Research Center, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1104, Houston, TX 77030, USA. Tel: +1 713 792 1637; Fax: +1 713 563 1185; E-mail: [email protected]
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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.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e30
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

Ongoing studies available for MPNST patients are provided as a service of the US National Institutes of Health:

Grobmyer, S.R. et al. (2008) Malignant peripheral nerve sheath tumor: molecular pathogenesis and current management considerations. Journal of Surgical Oncology 97, 340-349Google Scholar
Gupta, G., Mammis, A. and Maniker, A. (2008) Malignant peripheral nerve sheath tumors. Neurosurgery Clinics of North America 19, 533-543Google Scholar
Rubin, J.B. and Gutmann, D.H. (2005) Neurofibromatosis type 1 – a model for nervous system tumour formation? Nature Reviews Cancer 5, 557-564Google Scholar
Gschwind, A., Fischer, O.M. and Ullrich, A. (2004) The discovery of receptor tyrosine kinases: targets for cancer therapy. Nature Reviews Cancer 4, 361-370Google Scholar
Sebolt-Leopold, J.S. and Herrera, R. (2004) Targeting the mitogen-activated protein kinase cascade to treat cancer. Nature Reviews Cancer 4, 937-947Google Scholar
Sabatini, D.M. (2006) mTOR and cancer: insights into a complex relationship. Nature Reviews Cancer 6, 729-734Google Scholar
http://clinicaltrials.gov/ct2/results?cond=%22Nerve+Sheath+Neoplasms%22Google Scholar
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