Gorde:
| Egile Nagusiak: | , , , , , , , , , |
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| Formatua: | Recurso digital |
| Hizkuntza: | ingelesa |
| Argitaratua: |
Zenodo
2025
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| Gaiak: | |
| Sarrera elektronikoa: | https://doi.org/10.5281/zenodo.17746451 |
| Etiketak: |
Etiketa erantsi
Etiketarik gabe, Izan zaitez lehena erregistro honi etiketa jartzen!
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Aurkibidea:
- <p><strong><span lang="EN-US">Abstract— </span></strong><span lang="EN-US">Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder resulting from NF1 gene mutations that cause constitutive activation of the RAS/MAPK signaling pathway. This dysregulation promotes the development of plexiform neurofibromas (PNs), benign tumors associated with notable morbidity when inoperable. This review<span> </span>summarizes<span> </span>advances<span> </span>in<span> </span>novel targeted therapies of NF1-associated PNs,<span> </span>focusing<span> </span>on<span> </span>MEK<span> </span>inhibitors<span> </span>with<span> </span>emphasis<span> </span>on<span> </span>selumetinib<span> </span>and<span> </span>mirdametinib.<span> </span>A<span> </span>systematic literature search was performed using PubMed, ResearchGate, and Google Scholar for studies published up to July 2025, complemented by manual reference<span> </span>screening.<span> </span>MEKis<span> </span>suppress<span> </span>MEK1/2<span> </span>activity,<span> </span>thereby<span> </span>attenuating<span> </span>aberrant<span> </span>RAS/MAPK<span> </span>signaling and<span> </span>tumor<span> </span>growth.<span> </span>Selumetinib,<span> </span>approved<span> </span>by<span> </span>the<span> </span>U.S.<span> </span>Food<span> </span>and<span> </span>Drug<span> </span>Administration<span> </span>(FDA)<span> </span>in<span> </span>2020<span> </span>for<span> </span>pediatric<span> </span>NF1-PNs,<span> </span>achieved a ≥20% tumor volume reduction in 74% of patients and yielded significant improvements in pain<span> </span>and<span> </span>quality<span> </span>of<span> </span>life.<span> </span>Mirdametinib, approved in 2025 for both pediatric<span> </span>and<span> </span>adult<span> </span>populations,<span> </span>demonstrated<span> </span>a<span> </span>median<span> </span>41%<span> </span>tumor<span> </span>reduction<span> </span>and<span> </span>sustained<span> </span>symptomatic benefit. The principal toxicities included dermatologic, gastrointestinal, ocular, and cardiac events, generally manageable with dose adjustment and monitoring. Despite substantial clinical benefit, unresolved challenges include long-term safety, optimal dosing,<span> </span>and the integration of MEK inhibition with surgical and multimodal approaches.<span> </span>Future<span> </span>research<span> </span>should<span> </span>focus<span> </span>on<span> </span>combination<span> </span>therapies and<span> </span>refinement<span> </span>of<span> </span>individualized<span> </span>treatment<span> </span>strategies.<span> </span>MEK<span> </span>inhibitors<span> </span>represent<span> </span>a<span> </span>major<span> </span>therapeutic<span> </span>breakthrough<span> </span>for NF1-associated PNs, offering durable tumor control, functional improvement, and new opportunities for precision medicine in neurofibromatosis care.</span></p> <p><strong><span lang="EN-US"> </span></strong></p> <p><strong><span lang="EN-US">Keywords</span></strong><span lang="EN-US">—<span> </span>neurofibromatosis,<span> </span>neurofibromatosis<span> </span>type<span> </span>1,<span> </span>NF1,<span> </span>plexiform<span> </span>neurofibroma,<span> </span>MEK<span> </span>inhibitors;<span> </span>targeted<span> </span>therapy,<span> </span>selumetinib,<span> </span><span>mirdametinib</span></span></p>