Anderson JL, Gutmann DH. Neurofibromatosis type 1. Handb Clin Neurol. 2015;132:75–86.
Martin GA, et al. The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21. Cell. 1990;63:843–9.
Article CAS PubMed Google Scholar
Basu TN, et al. Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature. 1992;356:713–5.
Article CAS PubMed Google Scholar
DeClue JE, et al. Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis. Cell. 1992;69:265–73.
Article CAS PubMed Google Scholar
Trovó-Marqui A, Tajara E. Neurofibromin: a general outlook. Clin Genet. 2006;70:1–13.
Gutmann DH, et al. Neurofibromatosis type 1. Nat Rev Dis Primer. 2017;3:17004.
Spyk SL, Thomas N, Cooper DN, Upadhyaya M. Neurofibromatosis type 1-associated tumours: their somatic mutational spectrum and pathogenesis. Hum Genomics. 2011;5:623–90.
Article CAS PubMed Central Google Scholar
Le LQ, et al. Susceptible stages in Schwann cells for NF1-associated plexiform neurofibroma development. Cancer Res. 2011;71:4686–95.
Article CAS PubMed PubMed Central Google Scholar
Zhu Y, Ghosh P, Charnay P, Burns DK, Parada LF. Neurofibromas in NF1: Schwann cell origin and role of tumor environment. Science. 2002;296:920–2.
Article CAS PubMed PubMed Central Google Scholar
Packer RJ, et al. Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference. Neuro-Oncol. 2020;22:773–84.
Article PubMed PubMed Central Google Scholar
Kresbach C, et al. Atypical neurofibromas reveal distinct epigenetic features with proximity to benign peripheral nerve sheath tumor entities. Neuro-Oncol. 2023;25:1644–55.
Article CAS PubMed PubMed Central Google Scholar
• Rhodes SD, et al. Cdkn2a (Arf) loss drives NF1-associated atypical neurofibroma and malignant transformation. Hum Mol Genet. 2019;28:2752–62. (This is an important study that defines the molecular mechanisms underlying malignant transformation of NF-1-associated plexiform neurofibromas to malignant peripheral nerve sheath tumors.)
Article CAS PubMed PubMed Central Google Scholar
Tong S, Devine WP, Shieh JT. Tumor and constitutional sequencing for neurofibromatosis type 1. JCO Precis Oncol. 2022;6:e2100540.
Article PubMed PubMed Central Google Scholar
Mitchell DK, et al. Spatial gene expression profiling unveils immuno-oncogenic programs of NF1-associated peripheral nerve sheath tumor progression. Clin Cancer Res Off J Am Assoc Cancer Res. 2023. https://doi.org/10.1158/1078-0432.CCR-23-2548.
Kahen EJ, et al. Neurofibromin level directs RAS pathway signaling and mediates sensitivity to targeted agents in malignant peripheral nerve sheath tumors. Oncotarget. 2018;9:22571–85.
Article PubMed PubMed Central Google Scholar
Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170:17–33.
Article CAS PubMed PubMed Central Google Scholar
Dombi E, et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med. 2016;375:2550–60.
Article CAS PubMed PubMed Central Google Scholar
• Gross AM, et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med. 2020;382:1430–42. (This clinical trial evaluating the efficacy of the MEK inhibitor selumetinib led to the FDA approval of selumetinib for symptomatic, inoperable plexiform neurofibromas in NF-1 pediatric patients.)
Article CAS PubMed PubMed Central Google Scholar
O’Sullivan Coyne GH, et al. Phase II trial of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886 Hydrogen Sulfate) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN). J Clin Oncol. 2020;38:3612–3612.
Bendell JC, et al. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017;116:575–83.
Article CAS PubMed PubMed Central Google Scholar
Fangusaro J, et al. Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol. 2019;20:1011–22.
Article CAS PubMed PubMed Central Google Scholar
Ma Y, et al. A molecular basis for neurofibroma-associated skeletal manifestations in NF1. Genet Med Off J Am Coll Med Genet. 2020;22:1786–93.
Walsh KS, et al. Impact of MEK inhibitor therapy on neurocognitive functioning in NF1. Neurol Genet. 2021;7:e616.
Article PubMed PubMed Central Google Scholar
Ciruela A, et al. Identification of MEK1 as a novel target for the treatment of neuropathic pain. Br J Pharmacol. 2003;138:751–6.
Article CAS PubMed PubMed Central Google Scholar
Ji RR, Baba H, Brenner GJ, Woolf CJ. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat Neurosci. 1999;2:1114–9.
Article CAS PubMed Google Scholar
Song Y, et al. Targeting RAS–RAF–MEK–ERK signaling pathway in human cancer: Current status in clinical trials. Genes Dis. 2022;10:76–88.
Article PubMed PubMed Central Google Scholar
Degirmenci U, Yap J, Sim YRM, Qin S, Hu J. Drug resistance in targeted cancer therapies with RAF inhibitors. Cancer Drug Resist. 2021;4:665–83.
CAS PubMed PubMed Central Google Scholar
• Kilburn LB, et al. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024;30:207–17. (This is an important clinical trial demonstrating response in heavily pre-treated pediatric patients with BRAF-altered low-grade glioma that has implications for patients with NF1-associated low-grade gliomas.)
Article CAS PubMed Google Scholar
Sigaud R, et al. The first-in-class ERK inhibitor ulixertinib shows promising activity in mitogen-activated protein kinase (MAPK)-driven pediatric low-grade glioma models. Neuro-Oncol. 2022;25:566–79.
Article PubMed Central Google Scholar
Flint AC, et al. Combined CDK4/6 and ERK1/2 inhibition enhances antitumor activity in NF1-associated plexiform neurofibroma. Clin Cancer Res. 2023;29:3438–56.
Article CAS PubMed PubMed Central Google Scholar
Boga SB, et al. MK-8353: Discovery of an orally bioavailable dual mechanism ERK inhibitor for oncology. ACS Med Chem Lett. 2018;9:761–7.
Article CAS PubMed PubMed Central Google Scholar
Stathis A, et al. Results of an open-label phase 1b study of the ERK inhibitor MK-8353 plus the MEK inhibitor selumetinib in patients with advanced or metastatic solid tumors. Invest New Drugs. 2023;41:1–11.
Bok S, et al. MEKK2 mediates aberrant ERK activation in neurofibromatosis type I. Nat Commun. 2020;11:5704.
Article CAS PubMed PubMed Central Google Scholar
Yang Y, Li S, Wang Y, Zhao Y, Li Q. Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective. Signal Transduct Target Ther. 2022;7:1–36.
Ferguson MJ, et al. Preclinical evidence for the use of sunitinib malate in the treatment of plexiform neurofibromas. Pediatr Blood Cancer. 2016;63:206–13.
Article CAS PubMed Google Scholar
Study Details | Study of Sutent®/Sunitinib (SU11248) in subjects with NF-1 plexiform neurofibromas | ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT01402817.
Robertson KA, et al. Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial. Lancet Oncol. 2012;13:1218–24.
Article CAS PubMed PubMed Central Google Scholar
Kim A, et al. Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas. Pediatr Blood Cancer. 2013;60:396–401.
Article CAS PubMed Google Scholar
Solares I, Viñal D, Morales-Conejo M, Rodriguez-Salas N, Feliu J. Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas: a comprehensive review. ESMO Open. 2021;6:100223.
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