Gross Andrea M, Dombi Eva, Widemann Brigitte C
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Building 10, Room 1-3752, Bethesda, MD, 20892, USA.
Childs Nerv Syst. 2020 Oct;36(10):2443-2452. doi: 10.1007/s00381-020-04731-2. Epub 2020 Jun 30.
Neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (pNF) can be debilitating and until recently, surgery was the only potentially effective therapy for these tumors.
We review critical steps in the path towards the FDA approval of the first medical therapy for NF1 pNF and the current status of MEK inhbitor therapy.
Sustained efforts by the NF community have resulted in a detailed understanding of the natural history and biology of NF1-related peripheral nerve sheath tumors. This work provided the basis for the development of meaningful clinical trials targeting pNF. Inhibition of the RAS/MAPK signaling pathway with MEK inhibitors identified the first medical therapy which resulted in shrinkage in the majority of children with NF1 and large inoperable pNF. Based on this finding and subsequent demonstration of clinical benefit, the MEK inhibitor selumetinib recently received approval by the United States Food and Drug Administration (FDA) for children with symptomatic pNF.
Sustained efforts and collaborations have resulted in identification of MEK inhibitors as effective therapy for NF1 pNF. Future work work will be directed at prevention of pNF morbidity and deepening the reponse in symptomatic pNF.
1型神经纤维瘤病（NF1）相关的丛状神经纤维瘤（pNF）可导致机体衰弱，直到最近，手术仍是针对这些肿瘤的唯一可能有效的治疗方法。
我们回顾了首个用于NF1 pNF的药物疗法获得美国食品药品监督管理局（FDA）批准过程中的关键步骤以及MEK抑制剂疗法的现状。
NF领域的持续努力使人们对NF1相关的周围神经鞘瘤的自然病史和生物学特性有了详细了解。这项工作为开展针对pNF的有意义的临床试验奠定了基础。用MEK抑制剂抑制RAS/MAPK信号通路确定了首个药物疗法，该疗法使大多数患有NF1和无法手术切除的大型pNF的儿童肿瘤缩小。基于这一发现及随后证实的临床获益，MEK抑制剂司美替尼最近获得美国食品药品监督管理局（FDA）批准，用于治疗有症状的pNF儿童患者。
持续的努力与合作已确定MEK抑制剂是治疗NF1 pNF的有效疗法。未来的工作将致力于预防pNF的发病，并加深对有症状pNF的反应。
