Critical role of PTEN for development and progression of nerve sheath tumors in neurofibromatosis type 1

2010 ◽  
Vol 6 (4) ◽  
pp. 499-501 ◽  
Author(s):  
Christian Mawrin
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Critical Role ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumors ◽  
Nerve Sheath

scholarly journals New Model Systems and the Development of Targeted Therapies for the Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 477 ◽  
Author(s):  
Kyle B. Williams ◽  
David A. Largaespada
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Single Agent ◽  
Neurofibromatosis Type ◽  
Mek Inhibitors ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

Neurofibromatosis Type 1 (NF1) is a common genetic disorder and cancer predisposition syndrome (1:3000 births) caused by mutations in the tumor suppressor gene NF1. NF1 encodes neurofibromin, a negative regulator of the Ras signaling pathway. Individuals with NF1 often develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage, some of which progress further to malignant peripheral nerve sheath tumors (MPNSTs). Treatment options for neurofibromas and MPNSTs are extremely limited, relying largely on surgical resection and cytotoxic chemotherapy. Identification of novel therapeutic targets in both benign neurofibromas and MPNSTs is critical for improved patient outcomes and quality of life. Recent clinical trials conducted in patients with NF1 for the treatment of symptomatic plexiform neurofibromas using inhibitors of the mitogen-activated protein kinase (MEK) have shown very promising results. However, MEK inhibitors do not work in all patients and have significant side effects. In addition, preliminary evidence suggests single agent use of MEK inhibitors for MPNST treatment will fail. Here, we describe the preclinical efforts that led to the identification of MEK inhibitors as promising therapeutics for the treatment of NF1-related neoplasia and possible reasons they lack single agent efficacy in the treatment of MPNSTs. In addition, we describe work to find targets other than MEK for treatment of MPNST. These have come from studies of RAS biochemistry, in vitro drug screening, forward genetic screens for Schwann cell tumors, and synthetic lethal screens in cells with oncogenic RAS gene mutations. Lastly, we discuss new approaches to exploit drug screening and synthetic lethality with NF1 loss of function mutations in human Schwann cells using CRISPR/Cas9 technology.

scholarly journals MicroRNAome profiling in benign and malignant neurofibromatosis type 1-associated nerve sheath tumors: evidences of PTEN pathway alterations in early NF1 tumorigenesis

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 473 ◽  
Author(s):  
Julien Masliah-Planchon ◽  
Eric Pasmant ◽  
Armelle Luscan ◽  
Ingrid Laurendeau ◽  
Nicolas Ortonne ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumors ◽  
Nerve Sheath

scholarly journals An Imprinted Locus Epistatically Influences Nstr1 and Nstr2 to Control Resistance to Nerve Sheath Tumors in a Neurofibromatosis Type 1 Mouse Model

2006 ◽  
Vol 66 (1) ◽  
pp. 62-68 ◽  
Author(s):  
Karlyne M. Reilly ◽  
Karl W. Broman ◽  
Roderick T. Bronson ◽  
Shirley Tsang ◽  
Dagan A. Loisel ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumors ◽  
Nerve Sheath

Neurofibromatosis-associated nerve sheath tumors

2006 ◽  
Vol 20 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Judith A. Murovic ◽  
Daniel H. Kim ◽  
David G. Kline
Keyword(s):  
Diagnostic Criteria ◽  
Current Literature ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Imaging Findings ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Examination Protocol ◽  
Nerve Sheath

In this paper the authors describe a patient with neurofibromatosis Type 1 (NF1) who presented with sequelae of this disease. They also review the current literature on NF1 and NF2 published between 2001 and 2005. The method used to obtain information for the case report consisted of a family member interview and a review of the patient's chart. For the literature review the authors used the search engine Ovid Medline to identify papers published on the topic between 2001 and 2005. Neurofibromatosis Type 1 appears in approximately one in 2500 to 4000 births, is caused by a defect on 17q11.2, and results in neurofibromin inactivation. The authors reviewed the current literature with regard to the following aspects of this disease: 1) diagnostic criteria for NF1; 2) criteria for other NF1-associated manifestations; 3) malignant peripheral nerve sheath tumors (PNSTs); 4) the examination protocol for a patient with an NF1-related NST; 5) imaging findings in patients with NF1; 6) other diagnostic studies; 7) surgical and adjuvant treatment for NSTs and malignant PNSTs; and 8) hormone receptors in NF1-related tumors. Pertinent illustrations are included. Neurofibromatosis Type 2 occurs much less frequently than NF1, that is, in one in 33,000 births. Mutations in NF2 occur on 22q12 and result in inactivation of the tumor suppressor merlin. The following data on this disease are presented: 1) diagnostic criteria for NF2; 2) criteria for other NF2 manifestations; 3) malignant PNSTs in patients with NF2; 4) examination protocol for the patient with NF2 who has an NST; and 5) imaging findings in patients with NF2. Relevant illustrations are included. It is important that neurosurgeons be aware of the sequelae of NF1 and NF2, because they may be called on to treat these conditions.

scholarly journals Nerve Sheath Tumors in Neurofibromatosis Type 1: Assessment of Whole-Body Metabolic Tumor Burden Using F-18-FDG PET/CT

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0143305 ◽  
Author(s):  
Johannes Salamon ◽  
László Papp ◽  
Zoltán Tóth ◽  
Azien Laqmani ◽  
Ivayla Apostolova ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Tumor Burden ◽  
Whole Body ◽  
Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Metabolic Tumor Burden
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