Review
Oncology
Ayesha Hassan, Roberto Carmagnani Pestana, Amanda Parkes
Summary: Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that pose a therapeutic challenge due to lack of effective targeted therapy. Although standard chemotherapy regimens exist, there is a particular need for novel therapeutic strategies, especially for neurofibromatosis type 1 (NF1)-associated MPNST.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2021)
Article
Clinical Neurology
Hiroshi Koike, Yoshihiro Nishida, Shinji Ito, Yoshie Shimoyama, Kunihiro Ikuta, Hiroshi Urakawa, Tomohisa Sakai, Koki Shimizu, Kan Ito, Shiro Imagama
Summary: There are significant differences between MPNST and pNF in terms of tumor size, peripheral enhancement pattern, perilesional edema-like zone, and intratumoral cystic change. The ADC values were significantly lower in MPNST compared to pNF, and setting a cutoff value of mean ADC at 1.85 x 10(-)(3) mm(2)/s provided sensitivity of 80% and specificity of 74%. Adding ADC evaluation to standard MRI evaluation improved the diagnostic accuracy.
WORLD NEUROSURGERY
(2022)
Article
Orthopedics
Sarah Attia, Mina Guirguis, Lu Q. Le, Avneesh Chhabra
Summary: This study suggests that there is no predisposition for pNFs and dNFs to develop into MPNSTs in NF1 patients. Therefore, these lesions may not require special surveillance compared to discrete peripheral nerve sheath tumors.
SKELETAL RADIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Bandarigoda N. Somatilaka, Ali Sadek, Renee M. McKay, Lu Q. Le
Summary: This article provides an overview of the biology and genetics of malignant peripheral nerve sheath tumors (MPNSTs), discusses research findings regarding their developmental origin, summarizes the various model systems used to study MPNSTs, and discusses current management strategies and recent developments in translating basic research findings into potential therapies.
Article
Health Care Sciences & Services
Garrett Alewine, Jerrica Knight, Adithya Ghantae, Christina Mamrega, Bashnona Attiah, Robert A. Coover, Cale D. Fahrenholtz
Summary: Neurofibromatosis type 1 (NF1) is a common neurogenic disorder characterized by loss of function mutations in the neurofibromin gene. Recent research has found that nanomedicine, specifically silver nanoparticles (AgNPs), shows promise in the treatment of NF1-associated malignant peripheral nerve sheath tumors (MPNSTs). AgNPs exhibit selective cytotoxicity towards NF1-associated MPNSTs and this sensitivity is correlated with the expression levels of functional neurofibromin. The use of AgNPs in co-culture with Schwann cells can selectively eradicate NF1-associated MPNSTs at doses tolerable to normal cells.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Oncology
Catena Kresbach, Matthias Dottermusch, Alicia Eckhardt, Inka Ristow, Petros Paplomatas, Lea Altendorf, Annika K. Wefers, Michael Bockmayr, Sarra Belakhoua, Ivy Tran, Lara Pohl, Sina Neyazi, Helena Bode, Said Farschtschi, Lennart Well, Reinhard E. Friedrich, David Reuss, Matija Snuderl, Christian Hagel, Victor-Felix Mautner, Ulrich Schueller
Summary: The study found that ANF with different histological morphologies exhibit distinct epigenetic similarities and cluster in proximity to benign peripheral nerve sheath tumor entities. Correlating this methylation pattern with clinical outcomes may be important for further understanding the malignant transformation mechanisms of ANF.
Article
Oncology
Yihui Gu, Wei Wang, Yuehua Li, Haibo Li, Zizhen Guo, Chengjiang Wei, Manmei Long, Manhon Chung, Rehanguli Aimaier, Qingfeng Li, Zhichao Wang
Summary: Malignant peripheral nerve sheath tumors (MPNSTs) are rare and difficult to treat soft-tissue sarcomas. This study evaluated different MEK inhibitors for the treatment of MPNSTs, and found that p-ERK can serve as a biomarker for predicting prognosis and an effective therapeutic target. Trametinib was identified as the most potent MEK inhibitor for the treatment of MPNSTs.
FRONTIERS IN ONCOLOGY
(2022)
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
Oncology
Nicolas Bachmann, Dominic Leiser, Alessia Pica, Barbara Bachtiary, Damien C. Weber
Summary: This study analyzed the outcomes of (m)PNST patients treated with proton therapy and PBS delivery paradigm. The results showed that PBSPT resulted in favorable oncologic outcomes and low toxicity rates in patients with (m)PNST.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Chengjun Yao, Haiying Zhou, Yanzhao Dong, Ahmad Alhaskawi, Sohaib Hasan Abdullah Ezzi, Zewei Wang, Jingtian Lai, Vishnu Goutham Kota, Mohamed Hasan Abdulla Hasan Abdulla, Hui Lu
Summary: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma with limited treatment options and a poor prognosis. This review summarizes the current understanding of MPNST pathogenesis and the latest advancements in diagnosis, treatment, and targeted therapies. The challenges and prospects for MPNST management are also discussed.
Review
Oncology
Jun Liu, Jing-Ning Huang, Ming-Han Wang, Zhen-Yang Ni, Wei-Hao Jiang, Manhon Chung, Cheng-Jiang Wei, Zhi-Chao Wang
Summary: This review summarizes current studies on different imaging methods for differentiating benign and malignant tumors in NF1. Pathological evaluation is the gold standard for diagnosis, but the invasive nature restricts its application. Non-invasive methods like CT and MRI are commonly used for tumor evaluation in NF1 patients. However, there is no consensus on screening the malignant transformation of benign tumors, and novel technologies like radiogenomics and PET-MRI have not been fully adopted.
FRONTIERS IN ONCOLOGY
(2022)
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.
Review
Oncology
Jordan Jones, Sarah Cain, Jonathan Pesic-Smith, Peter F. M. Choong, Andrew P. Morokoff, Kate J. Drummond, Gabriel Dabscheck
Summary: The main cause of early death in NF1 patients is MPNST. Current methods for diagnosis and monitoring are inadequate, but ctDNA shows promise in improving patient care.
JOURNAL OF NEURO-ONCOLOGY
(2021)
Review
Medicine, General & Internal
Gaetano Magro, Giuseppe Broggi, Giuseppe Angelico, Lidia Puzzo, Giada Maria Vecchio, Valentina Virzi, Lucia Salvatorelli, Martino Ruggieri
Summary: Peripheral nerve sheath tumors include a range of lesions with different biological behavior, such as neurofibromas, schwannomas, and perineuriomas. These tumors can occur as isolated lesions or in association with other neurofibromatosis or schwannomatosis. Malignant peripheral nerve sheath tumors are soft tissue sarcomas that may arise from a peripheral nerve or pre-existing neurofibromas.
Article
Pediatrics
Samantha W. E. Knight, Tristan E. Knight, Teresa Santiago, Andrew J. Murphy, Abdelhafeez H. Abdelhafeez
Summary: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with nerve sheath differentiation. They have a tendency to metastasize and are relatively common in individuals with neurofibromatosis type 1. The staging of MPNSTs is complex and requires multi-disciplinary collaboration. Surgical management is the primary approach, with non-surgical modalities playing a supportive role. Advances in molecular characterization have allowed the integration of targeted inhibitors into MPNST management.
Article
Oncology
Amanda De Andrade Costa, Jit Chatterjee, Olivia Cobb, Shilpa Sanapala, Suzanne Scheaffer, Xiaofan Guo, Sonika Dahiya, David H. Gutmann
Summary: The study identified ITGAL/CD11A as a critical microglia regulator of LGG biology, with implications for future stroma-targeted brain tumor treatment strategies.
Article
Cell Biology
Corina Anastasaki, Paola Orozco, David H. Gutmann
Summary: Neurofibromatosis type 1 is a rare neurogenetic syndrome caused by mutations in the NF1 gene. The encoded protein, neurofibromin, functions as a negative regulator of RAS activity. However, neurofibromin may have additional functions beyond the canonical RAS pathway regulation.
DISEASE MODELS & MECHANISMS
(2022)
Review
Pharmacology & Pharmacy
Simge Acar, Amy E. Armstrong, Angela C. Hirbe
Summary: NF1 is a genetic condition leading to PN, with surgery as main treatment and MEKi showing efficacy for inoperable PN. Further studies are needed to fully understand MEKi's clinical application and evaluate other potential therapies.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Oncology
Elizabeth C. Cordell, Mahmoud S. Alghamri, Maria G. Castro, David H. Gutmann
Summary: The brain tumor microenvironment contains various nonneoplastic cells, which play important roles in the formation and progression of brain cancers. This review discusses the roles of T cells in low- and high-grade glioma formation and progression, as well as the potential uses of modified T lymphocytes for brain cancer therapeutics.
Article
Multidisciplinary Sciences
Corina Anastasaki, Juan Mo, Ji-Kang Chen, Jit Chatterjee, Yuan Pan, Suzanne M. Scheaffer, Olivia Cobb, Michelle Monje, Lu Q. Le, David H. Gutmann
Summary: Neuronal activity plays a crucial role in central and peripheral nervous system cancers. NF1 mutations modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production. In mouse models, reduced HCN channel function driven by Nf1 mutations leads to tumor growth in both central and peripheral nervous system.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Alice F. Bewley, Titilope M. Akinwe, Tychele N. Turner, David H. Gutmann
Summary: NF1 variants in sporadic tumors differ from those in NF1 individuals in terms of type, location, and pathogenicity. Many NF1 variants in sporadic cancers are not pathogenic and may be passenger variants or hypomorphic alleles. Further research is needed to define their roles in nonsyndromic cancer.
NEUROLOGY-GENETICS
(2022)
Review
Clinical Neurology
Simge Acar, Edwin Nieblas-Bedolla, Amy E. Armstrong, Angela C. Hirbe
Summary: Recent and ongoing clinical trials have mainly focused on patients with NF1 and the treatment of PNs. This research has resulted in the first FDA-approved drug for NF1-PN and has changed the approach to managing these tumors, allowing for systemic therapy instead of relying solely on surgery. Trials evaluating comorbid psychiatric conditions and quality of life among NF patients appear to be less common. These areas may require more attention in future studies to enhance clinical management.
PEDIATRIC NEUROLOGY
(2022)
Article
Genetics & Heredity
Lawrence Liu, Carina Dehner, Nikhil Grandhi, Yang Lyu, Dana C. Borcherding, John S. A. Chrisinger, Xiao Zhang, Jingqin Luo, Yu Tao, Amanda Parkes, Nam Q. Bui, Elizabeth J. Davis, Mohammed M. Milhem, Varun Monga, Mia Weiss, Brian Van Tine, Angela C. Hirbe
Summary: This study investigated the impact of genetic mutations in PEComa patients on treatment response, and found no significant association between gene mutations and survival rate or progression-free survival after treatment. Further research should focus on identifying other TSC-1/-2 silencing driver genes to predict response to mTOR inhibition therapy.
Article
Oncology
Alex T. Larsson, Himanshi Bhatia, Ana Calizo, Kai Pollard, Xiaochun Zhang, Eric Conniff, Justin F. Tibbitts, Elizabeth Rono, Katherine Cummins, Sara H. Osum, Kyle B. Williams, Alexandra L. Crampton, Tyler Jubenville, Daniel Schefer, Kuangying Yang, Yang Lyu, James C. Pino, Jessica Bade, John M. Gross, Alla Lisok, Carina A. Dehner, John S. A. Chrisinger, Kevin He, Sara J. C. Gosline, Christine A. Pratilas, David A. Largaespada, David K. Wood, Angela C. Hirbe
Summary: This study successfully established an innovative 3D platform for drug discovery and biological exploration of malignant peripheral nerve sheath tumors (MPNST). By utilizing patient-derived xenografts (PDX) and 3D microtissues, they accurately captured the genomic diversity of MPNST and validated the consistency of drug response in vivo and ex vivo.
Article
Medicine, General & Internal
Natalie K. Heater, Scott Okuno, Steven Robinson, Steven Attia, Mahesh Seetharam, Brittany L. Siontis, Janet Yoon, Sant Chawla, Mohammed M. Milhem, Varun Monga, Keith Skubitz, John Charlson, Angela C. Hirbe, Mia C. Weiss, Brian Van Tine, Mark Agulnik
Summary: The treatment of sarcoma requires a collaborative multidisciplinary approach due to its rarity and complexity. At a single institution, teams of specialists from various disciplines determine and implement treatment plans involving surgery, radiation, and medication. Recent advancements in systemic therapies for advanced or nonresectable soft tissue sarcoma, such as immunotherapies and targeted therapies, have improved treatment guidelines. Collaboration between institutions is crucial to facilitate enrollment in clinical trials. This article describes the success of the Midwest Sarcoma Trials Partnership (MWSTP) in establishing a network that includes academic centers and community sites, and proposes a new model using online platforms to expand access to clinical expertise in the treatment of advanced soft tissue sarcoma.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Nam Bui, Hilary Dietz, Sheima Farag, Angela C. Hirbe, Michael J. Wagner, Brian A. Van Tine, Kristen Ganjoo, Robin L. Jones, Vicki L. Keedy, Elizabeth J. Davis
Summary: This study retrospectively analyzed the clinical characteristics and outcomes of 74 patients with dedifferentiated chondrosarcoma (DDCS). Most patients presented with localized disease and underwent surgical resection as the main treatment. Chemotherapy was mainly used for metastatic cases, with partial responses observed in a small number of patients treated with doxorubicin with cisplatin or ifosfamide and single-agent pembrolizumab. Other regimens resulted in stable disease as the best response. Prolonged stable disease was achieved with pazopanib and immune checkpoint inhibitors. Due to the poor outcomes and limited benefit of conventional chemotherapy in DDCS, future studies should focus on the role of molecularly targeted therapies and immunotherapy.
Article
Oncology
Till Milde, Jason Fangusaro, Michael J. Fisher, Cynthia Hawkins, Fausto J. Rodriguez, Uri Tabori, Olaf Witt, Yuan Zhu, David H. Gutmann
Summary: Pediatric low-grade gliomas (pLGGs) are common brain tumors in young children, which often result in chronic tumor- and therapy-related morbidities. The growth of pLGGs is influenced by genetic alterations and nonneoplastic cells in the microenvironment. Preclinical models are necessary to identify potential drugs for clinical evaluation and improve treatment for children with pLGGs.
Editorial Material
Medicine, Research & Experimental
David H. Gutmann
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Review
Oncology
Yunshuo Tang, David H. Gutmann
Summary: Optic pathway glioma (OPG) occurs in a significant number of individuals with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. While often benign and slow growing, some patients with NF1-OPGs experience symptoms such as vision loss and precocious puberty. Studies using genetically engineered Nf1-OPG mouse models have provided valuable insights into the molecular and cellular pathways of optic gliomagenesis and identified potential new treatments. Research focusing on determining the factors underlying optic glioma development and tumor-induced optic nerve injury will contribute to personalized risk assessment and improved treatment for children with NF1-OPG.
CANCER MANAGEMENT AND RESEARCH
(2023)
Article
Oncology
Nicole M. Brossier, Jennifer M. Strahle, Samuel J. Cler, Michael Wallendorf, David H. Gutmann
NEURO-ONCOLOGY ADVANCES
(2022)
