ArticleNeuro-oncology2011
Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2.
Article in Neuro-oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Contemporary Molecular Biology of Sporadic Vestibular Schwannomas: A Systematic Review and Clinical Implications.The journal of international advanced otology · 2018Pooled it
- The molecular biology of NF2/Merlin on tumorigenesis and development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Proteomic analysis of pleomorphic dermal sarcoma reveals a fibroblastic cell of origin and distinct immune evasion mechanisms.Scientific reports · 2024Article
- Drug target therapy and emerging clinical relevance of exosomes in meningeal tumors.Molecular and cellular biochemistry · 2024Review
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Advances in Targeted Therapy for Neurofibromatosis Type 2 (NF2)-Associated Vestibular Schwannomas.Current oncology reports · 2023Review
- [Research progress on non-surgical treatment of vestibular schwannomas].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2022Review
- [Prospects of Drug Therapy of Vestibular Schwannoma].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Review
- A Critical Overview of Targeted Therapies for Vestibular Schwannoma.International journal of molecular sciences · 2022Review
- Qu-Du-San-Jie decoction induces growth inhibition and vascular normalization in NF2-associated vestibular schwannoma.Frontiers in pharmacology · 2022Article
- A Review of Drug Therapy in Vestibular Schwannoma.Drug design, development and therapy · 2021Review
- An update on the CNS manifestations of neurofibromatosis type 2.Acta neuropathologica · 2020Review
- Nonsteroidal sulfamate derivatives as new therapeutic approaches for Neurofibromatosis 2 (NF2).BMC pharmacology & toxicology · 2019Article
- Preclinical assessment of MEK1/2 inhibitors for neurofibromatosis type 2-associated schwannomas reveals differences in efficacy and drug resistance development.Neuro-oncology · 2019Article
- The efficacy of lapatinib and nilotinib in combination with radiation therapy in a model of NF2 associated peripheral schwannoma.Journal of neuro-oncology · 2017Article
- Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann cells.Oncotarget · 2017Article
- Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies.Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale · 2016Review
- Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.Neuro-oncology · 2016Review
- Role of Merlin/NF2 inactivation in tumor biology.Oncogene · 2016Review
- Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2.Journal of neuro-oncology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of the tumor suppressor merlin is a cause of frequent tumors of the nervous system, such as schwannomas, meningiomas, and ependymomas, which occur spontaneously or as part of neurofibromatosis type 2 (NF2). Because there is medical need for drug therapies for these tumors, our aim is to find therapeutic targets. We have studied the pathobiology of schwannomas, because they are the most common merlin-deficient tumors and are a model for all merlin-deficient tumors. With use of a human schwannoma in vitro model, we previously described strong overexpression/activation of platelet-derived growth factor receptor-β (PDGFR-β) leading to strong, long-lasting activation of extracellular-signal-regulated kinase (ERK1/2) and AKT and increased schwannoma growth, which we successfully inhibited using the PDGFR/Raf inhibitor sorafenib. However, the benign character of schwannomas may require long-term treatment; thus, drug tolerability is an issue. With the use of Western blotting, proliferation assays, viability assays, and a primary human schwannoma cell in vitro model, we tested the PDGFR/c-KIT inhibitors imatinib (Glivec(;) Novartis) and nilotinib (Tasigna(;) Novartis). Imatinib and nilotinib inhibited PDGF-DD-mediated ERK1/2 activation, basal and PDGF-DD-mediated activation of PDGFR-β and AKT, and schwannoma proliferation. Nilotinib is more potent than imatinib, exerting its maximal inhibitory effect at concentrations lower than steady-state trough plasma levels. In addition, nilotinib combined with the MEK1/2 inhibitor selumetinib (AZD6244) at low concentrations displayed stronger efficiency toward tumor growth inhibition, compared with nilotinib alone. We suggest that therapy with nilotinib or combinational therapy that simultaneously inhibits PDGFR and the downstream Raf/MEK1/2/ERK1/2 pathway could represent an effective treatment for schwannomas and other merlin-deficient tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.