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Perspective | Open Access

Rare Disease and Orphan Drugs

Journal

Kim et al. Rare Dis Orphan Drugs J. 2026;5:6 DOI:10.20517/rdodj.2025.52

Plexiform neurofibromas in neurofibromatosis type

1: current and emergent therapeutic strategies

Hannah Kim , Julia Polen , Gurcharanjeet Kaur 3
1
2
Keywords: Abstract
Neurofibromatosis type 1,
plexiform neurofibroma, Neurofibromatosis type 1-associated plexiform neurofibromas cause significant morbidity
mitogen-activated protein and carry a risk of malignant transformation. Early targeted agents failed to demonstrate
kinase kinase inhibitors, efficacy, safety, or durable responses until the discovery of mitogen-activated protein
mitogen-activated protein kinase kinase (MEK 1/2) inhibitors. Selumetinib and mirdametinib are approved medical
kinase pathway, targeted
therapy therapies that can potentially reduce tumor volume and symptoms, improve
patient-reported outcomes, and have manageable toxicities. An indirect comparison
Citation: Kim H, Polen J, between selumetinib and mirdametinib suggests differences in efficacy and safety, but
Kaur G. Plexiform direct confirmatory head-to-head trials are needed. Active clinical trials in the pipeline are
neurofibromas in
neurofibromatosis type 1: exploring other targets in the MEK pathway, along with combination therapies. Key
current and emergent priorities include the impact of malignant peripheral nerve sheath tumor risk, defining
therapeutic strategies. Rare long-term safety, durability off therapy, predictors of response and resistance, and
Dis Orphan Drugs J. implementation of multidisciplinary care.
2026;5:6.
https://dx.doi.org/10.20517
/rdodj.2025.52
Received: 25 Aug 2025 INTRODUCTION
First Decision: 28 Nov Neurofibromatosis type 1 (NF1) is a rare neurogenetic disorder that affects
2025
[1]
Revised: 17 Dec 2025 approximately 1 in 2,500 individuals worldwide . This genetic defect causes a wide
Accepted: 29 Jan 2026 range of clinical manifestations, including, but not limited to, nervous system
Published: 2 Mar 2026 tumors, skeletal manifestations, vasculopathies, seizures, headaches, and learning

Academic Editor: disabilities. One hallmark manifestation of NF1 is the development of plexiform
Daniel Scherman neurofibromas (PNs), which occurs in 30%-60% of individuals with NF1 [1,2] .
Copy Editor: Although benign, PNs can cause substantial morbidity due to pain, motor or sensory
Fangling Lan
Production Editor: impairment, disfigurement, and compression of vital anatomical structures including
Fangling Lan the spinal cord, airway, or major blood vessels. More importantly, 8%-13% of the
PNs may transform into malignant peripheral nerve sheath tumors (MPNSTs), a
type of aggressive sarcoma associated with high morbidity and mortality rates .
[1]
Historically, treatment options have been limited to surgical resection, which carries
significant risk in many patients because of the location of the tumors. Recent
targeted therapies have introduced a new era of pharmacologic management.

1 William Carey University College of Osteopathic Medicine, Hattiesburg, MS 39401, USA.
2 School of Nursing, Elon University, Elon, NC 27244, USA.
3 Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.

Correspondence to: Dr. Gurcharanjeet Kaur, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032,
USA. E-mail: gk2626@cumc.columbia.edu

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