Article
Oncology
Rebecca Ronsley, Celine D. Hounjet, Sylvia Cheng, Shahrad Rod Rassekh, Walter J. Duncan, Christopher Dunham, Jane Gardiner, Arvindera Ghag, Jeffrey P. Ludemann, David Wensley, Wingfield Rehmus, Michael A. Sargent, Juliette Hukin
Summary: Six NF-1 patients were treated with trametinib, showing either partial response or stability in all cases, with generally well-tolerated adverse effects of grade 1-2 paronychia or dermatitis. Further data and clinical trials are needed to assess the efficacy and durability of this treatment method.
Review
Oncology
Amy E. Armstrong, Allan J. Belzberg, John R. Crawford, Angela C. Hirbe, Zhihong J. Wang
Summary: Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome caused by NF1 gene variants leading to loss of neurofibromin. Surgery is the traditional treatment for plexiform neurofibromas (PN) in NF1 patients, but some PN are inoperable. MEK1/2 inhibitor selumetinib has shown promising efficacy as a medical treatment option for pediatric patients with symptomatic, inoperable NF1-PN. Other MEK inhibitors and tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN.
Article
Oncology
Peter M. K. de Blank, Andrea M. Gross, Srivandana Akshintala, Jaishri O. Blakeley, Gideon Bollag, Ashley Cannon, Eva Dombi, Jason Fangusaro, Bruce D. Gelb, Darren Hargrave, AeRang Kim, Laura J. Klesse, Mignon Loh, Staci Martin, Christopher Moertel, Roger Packer, Jonathan M. Payne, Katherine A. Rauen, Jonathan J. Rios, Nathan Robison, Elizabeth K. Schorry, Kevin Shannon, David A. Stevenson, Elliot Stieglitz, Nicole J. Ullrich, Karin S. Walsh, Brian D. Weiss, Pamela L. Wolters, Kaleb Yohay, Marielle E. Yohe, Brigitte C. Widemann, Michael J. Fisher
Summary: Neurofibromatosis type 1 (NF1) is a genetic syndrome with a wide range of clinical manifestations driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) can block downstream targets of RAS. The recent approval of MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 has made it the first medical therapy approved for this indication. Clinical trials have shown potential benefits of MEKi for various other NF1 manifestations, and there is interest in their clinical use.
Article
Dermatology
Eran Cohen-Barak, Hagit Toledano-Alhadef, Nada Danial-Farran, Ido Livneh, Banan Mwassi, Maysa Hriesh, Fadia Zagairy, Chen Gafni-Amsalem, Husam Bashir, Morad Khayat, Nassim Warrour, Osnat Sher, Daphna Marom, Sergey Postovsky, Tal Dujovny, Michael Ziv, Stavit A. Shalev
Summary: The study identified germline mutations in NF1 and LZTR1 genes, as well as a somatic variant in GNAZ, in a 9-month-old NF1 patient with life-threatening plexiform neurofibroma. Cellular analysis revealed increased ERK 1/2 activation in cells expressing mutant GNAZ, suggesting a synergistic effect of NF1, LZRT1, and GNAZ variants contributing to the severity of the patient's condition. Treatment with the MEK inhibitor trametinib resulted in significant clinical improvement, supporting the use of targeted therapy based on individual genetic variations.
EXPERIMENTAL DERMATOLOGY
(2022)
Review
Chemistry, Medicinal
Dun Wang, Lingling Ge, Zizhen Guo, Yuehua Li, Beiyao Zhu, Wei Wang, Chengjiang Wei, Qingfeng Li, Zhichao Wang
Summary: This meta-analysis evaluated the effectiveness and safety of trametinib in treating NF1-related nerve tumors. The results showed that trametinib had a satisfactory ability to stabilize tumor progression but a more limited ability to shrink tumors. The safety profile of trametinib was satisfactory.
Article
Oncology
Michael J. Fisher, Jaishri O. Blakeley, Brian D. Weiss, Eva Dombi, Shivani Ahlawat, Srivandana Akshintala, Allan J. Belzberg, Miriam Bornhorst, Miriam A. Bredella, Wenli Cai, Rosalie E. Ferner, Andrea M. Gross, Gordon J. Harris, Robert Listernick, Ina Ly, Staci Martin, Victor F. Mautner, Johannes M. Salamon, Kilian E. Salerno, Robert J. Spinner, Verena Staedtke, Nicole J. Ullrich, Meena Upadhyaya, Pamela L. Wolters, Kaleb Yohay, Brigitte C. Widemann
Summary: Plexiform neurofibromas are a common manifestation of neurofibromatosis type 1, with surgery being the main treatment option in the past. However, recent regulatory approvals of the MEK inhibitor selumetinib have provided new options for PN management. Currently, there is no consensus on the definition, diagnostic evaluation, surveillance strategy, and treatment indications for PN. This review provides consensus recommendations from NF1 experts to address these questions.
Article
Clinical Neurology
Eddie Luidy Imada, Diego Strianese, Deepak P. Edward, Rawan AlThaqib, Antionette Price, Antje Arnold, Hailah Al-Hussain, Luigi Marchionni, Fausto J. Rodriguez
Summary: The study identified gene expression differences between orbitofacial NFs and NFs occurring at other locations, suggesting that orbitofacial NFs may have higher local aggressiveness and treatment challenges. Further investigation may be warranted given the disproportionate morbidity associated with orbitofacial NFs.
Editorial Material
Medicine, General & Internal
Antonella Cacchione, Alessia Carboni, Mariachiara Lodi, Rita De Vito, Andrea Carai, Antonio Marrazzo, Marina Macchiaiolo, Ioan Paul Voicu, Angela Mastronuzzi, Giovanna Stefania Colafati
Summary: Different radiographical imaging modalities were used to diagnose and evaluate the condition of a patient with NF1 and PN, biopsy confirmed the diagnosis. NF1 diagnosis at birth remains challenging, with congenital PN recognized in 20% of cases. Early detection of PN progression allowed for necessary life-saving interventions.
Article
Oncology
Reinhard E. Friedrich, Louisa K. N. Noernberg, Christian Hagel
Summary: This study aimed to characterize the growth pattern and antigen profile of peripheral nerve sheath tumors (PNST) in patients with Neurofibromatosis type 1 (NF1), with a focus on the morphological characteristics of diffuse plexiform neurofibroma (DPNF). The study found distinct cellular characteristics and differences in antigen expression among different types of PNST. The findings provide insight into the biological differences between these tumors.
ANTICANCER RESEARCH
(2022)
Review
Oncology
Dina Poplausky, Jade N. N. Young, Hansen Tai, Ryan Rivera-Oyola, Nicholas Gulati, Rebecca M. M. Brown
Summary: Neurofibromatosis type 1 (NF1) is a genetic neuroectodermal disorder associated with various skin findings, including cutaneous neurofibromas. There are limited treatment options for the cutaneous manifestations of NF1, and interdisciplinary collaboration is often necessary for the appropriate care of these patients. Increased awareness of NF1 and its dermatologic associations is important for providing adequate care to patients.
Article
Oncology
Chelsea Kotch, Kristina Wagner, J. Harris Broad, Eva Dombi, Jane E. E. Minturn, Peter Phillips, Katherine Smith, Yimei Li, Ian N. N. Jacobs, Lisa M. M. Elden, Michael J. J. Fisher, Jean Belasco
Summary: The study evaluated the efficacy of vinblastine and methotrexate in NF1-associated plexiform neurofibroma. The results showed that this treatment was effective in some patients, but 2D imaging was not sensitive enough for evaluating tumor volume.
Article
Medicine, General & Internal
Kunihiro Ikuta, Yoshihiro Nishida, Tomohisa Sakai, Hiroshi Koike, Kan Ito, Hiroshi Urakawa, Shiro Imagama
Summary: This study retrospectively reviewed surgical excision cases of deep-seated nodular plexiform neurofibromas in patients with neurofibromatosis type 1 and found that surgical treatment of these tumors is relatively safe with improvement in preoperative symptoms.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Clinical Neurology
Ike Iheanacho, Hyun Kyoo Yoo, Xiaoqin Yang, Sophie Dodman, Rachel Hughes, Suvina Amin
Summary: The purpose of the study is to investigate the epidemiology, burden of illness, and outcomes of surgical resection in pediatric patients with NF-1 and associated PNs. The results suggest that NF-1 is rare in children, but has increased morbidity and mortality in those with associated PNs. Surgical outcomes for PNs are often poor, indicating significant unmet needs in these patients.
NEUROLOGICAL SCIENCES
(2022)
Review
Oncology
Robert Galvin, Adrienne L. Watson, David A. Largaespada, Nancy Ratner, Sara Osum, Christopher L. Moertel
Summary: MEK inhibitors have shown efficacy for NF1-related conditions, such as plexiform neurofibromas and low-grade gliomas, with recent success seen in the use of selumetinib for inoperable plexiform neurofibroma. Ongoing investigations into combination therapy and the development of a representative NF1 swine model offer promise for future therapeutic translations for other NF1-related pathology.
CURRENT ONCOLOGY REPORTS
(2021)
Review
Oncology
Ling-Ling Ge, Ming-Yan Xing, Hai-Bing Zhang, Zhi-Chao Wang
Summary: This review summarizes the accumulating evidence on the cellular and molecular pathogenesis of neurofibroma development. Neurofibromatosis type 1 (NF1) is a genetic tumor predisposition syndrome that affects about 1 in 3000 newborns and is caused by mutations in the NF1 gene. The distinct characteristics of plexiform and cutaneous neurofibromas have prompted hypotheses about the origin and developmental features of these tumors.