title: Systemic therapy in neurofibromatosis type 2.
abstract: The systemic treatment of patients with neurofibromatosis type 2 associated tumours is challenging, as these patients often have prolonged survival but with the inevitable propensity for their disease to cause symptoms, and no effective therapies other than local treatments such as surgery. Understanding the molecular mechanisms driving NF-2 pathogenesis holds promise for the potential use of targeted therapy. Initial studies of agents such as bevacizumab (angiogenesis inhibitor) and lapatinib (epidermal growth factor and ErbB2 inhibitor) have indicated benefit for selected patients. As the biology of NF-2 is dependent on multiple interlinked downstream signalling pathways, targeting multiple pathways may be more effective than single agents. Phase zero trials, adaptive phase II or small multi-arm trials, are likely the way forward in this rare disease. Ideally, well-tolerated targeted therapy would appear to be the most promising approach for patients with NF-2, given the natural history of this disease.
authors.affiliation: Department of Medical Oncology and Ingham Research Institute, Liverpool, NSW, Australia. Electronic address: stephanie.lim@sswahs.nsw.gov.au.
authors.forename: Stephanie Hui-Su
authors.initials: SH
authors.lastname: Lim
authors.affiliation: TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Westmead, NSW, Australia. Electronic address: simone.ardernholmes@health.nsw.gov.au.
authors.forename: Simone
authors.initials: S
authors.lastname: Ardern-Holmes
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Westmead, NSW, Australia. Electronic address: geoff.mccowage@health.nsw.gov.au.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: McCowage
authors.affiliation: Department of Medical Oncology and Ingham Research Institute, Liverpool, NSW, Australia; University of Western Sydney, School of Medicine, Molecular Medicine Research Group, NSW, Australia. Electronic address: p.desouza@uws.edu.au.
authors.forename: Paul
authors.initials: P
authors.lastname: de Souza
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D000077341:Lapatinib; D058990:Molecular Targeted Therapy; D016518:Neurofibromatosis 2 / Q000188:drug therapy* / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000077341:Lapatinib; D000068258:Bevacizumab; D066246:ErbB Receptors
keywords: Neurofibromatosis type 2; Signal transduction; Tyrosine kinase inhibitors