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
Oncology
Sumanth Nagabushan, Loretta M. S. Lau, Paulette Barahona, Marie Wong, Alexandra Sherstyuk, Glenn M. Marshall, Vanessa Tyrrell, Eva A. Wegner, Paul G. Ekert, Mark J. Cowley, Chelsea Mayoh, Toby N. Trahair, Philip Crowe, Antoinette Anazodo, David S. Ziegler
Summary: The prognosis of recurrent malignant peripheral nerve sheath tumors (MPNST) is poor and surgical resection remains the main treatment option. Chemoradiation approaches have not significantly improved outcomes, while therapies targeting genomic drivers of MPNST have been unsuccessful. MEK inhibitors show promise in preclinical studies but clinical efficacy remains unknown.
NPJ PRECISION ONCOLOGY
(2021)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Ziyu Guo, Wei Liu, Ziqian Dong, Lan Yang, Peng Xie
Summary: This is a rare case of malignant peripheral nerve sheath tumor involving the solitary lumbar vertebra. The patient presented with growing lumbocrural pain for 2 months. CT scan revealed a solitary vertebral lesion, highly suggestive of metastatic malignancy. F-18-FDG PET/CT showed heterogeneous intense FDG accumulation in the vertebral lesion with an SUVmax of 16.4. Pathological examination confirmed the diagnosis of malignant peripheral nerve sheath tumor. This case highlights the importance of considering MPNST when there is solitary vertebra invasion with increased FDG uptake.
CLINICAL NUCLEAR MEDICINE
(2023)
Article
Acoustics
Zhenzhen Jin, Kaiping Zhao, Wen Guo, Dandan Wang, Yukun Deng, Tao Chen
Summary: This study aimed to differentiate malignant peripheral nerve sheath tumors (MPNSTs) from benign peripheral nerve sheath tumors (BPNSTs) using sonography. Key features were identified, and a scoring system was established. The results demonstrated the effectiveness of sonography in differentiating between MPNSTs and BPNSTs.
JOURNAL OF ULTRASOUND IN MEDICINE
(2022)
Article
Clinical Neurology
Megan C. Everson, Courtney Pendleton, Megan M. Jack, Brandon W. Smith, Jodi M. Carter, Robert J. Spinner
Summary: Malignant perineurioma is a rare subset of MPNST with distinct clinical features. Patients in the study had uncomplicated clinical courses post-diagnosis, but further research is needed to fully understand the clinical course of these rare tumors.
WORLD NEUROSURGERY
(2021)
Article
Clinical Neurology
Michael Zhang, Elizabeth Tong, Forrest Hamrick, Edward H. Lee, Lydia T. Tam, Courtney Pendleton, Brandon W. Smith, Nicholas F. Hug, Sandip Biswal, Jayne Seekins, Sarah A. Mattonen, Sandy Napel, Cynthia J. Campen, Robert J. Spinner, Kristen W. Yeom, Thomas J. Wilson, Mark A. Mahan
Summary: This study developed a machine learning approach using high-dimensional radiomics features and clinical data to differentiate benign from malignant peripheral nerve sheath tumors (PNSTs). The method achieved high specificity and AUC on the test set, outperforming human experts in tumor classification.
Article
Multidisciplinary Sciences
Jody Fromm Longo, Stephanie N. Brosius, Iya Znoyko, Victoria A. Alers, Dorea P. Jenkins, Robert C. Wilson, Andrew J. Carroll, Daynna J. Wolff, Kevin A. Roth, Steven L. Carro
Summary: This article introduces a new sporadic MPNST cell line, 2XSB, with molecular and genomic features similar to the parent tumor, providing a useful tool for investigating the biology and potential treatment regimens for sporadic MPNSTs. The cells display invasive capabilities and form solid tumors when xenografted into immunodeficient mice, and genomic analyses reveal mutations in key genes implicated in MPNST pathogenesis.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Teddy Mohamad, Camille Plante, Jean-Philippe Brosseau
Summary: This review article summarizes the natural history of malignant peripheral nerve sheath tumors (MPNSTs), discusses mouse models representing the progression to MPNST, explores the role of the tumor microenvironment in MPNST development, and examines the signaling pathways associated with MPNST development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Yoshihiro Nishida, Hiroshi Urakawa, Robert Nakayama, Eisuke Kobayashi, Toshifumi Ozaki, Keisuke Ae, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Takahiro Goto, Hiroaki Hiraga, Norifumi Naka, Shunji Takahashi, Yuichi Ando, Masahiko Ando, Yachiyo Kuwatsuka, Shunsuke Hamada, Takafumi Ueda, Akira Kawai
Summary: The study examined the efficacy of pazopanib against MPNST, demonstrating favorable clinical benefit, progression-free survival, and overall survival rates. Patients with higher FNCLCC grades showed better outcomes with pazopanib treatment.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Review
Radiology, Nuclear Medicine & Medical Imaging
Mitchell P. Wilson, Prayash Katlariwala, Gavin Low, Mohammad H. Murad, Matthew D. F. McInnes, Line Jacques, Andrew S. Jack
Summary: This systematic review and meta-analysis evaluated the diagnostic accuracy of MRI for differentiating malignant from benign peripheral nerve sheath tumors. The study found that combining features such as diffusion restriction can optimize the diagnostic accuracy of MRI for detecting MPNSTs.
AMERICAN JOURNAL OF ROENTGENOLOGY
(2021)
Article
Oncology
Xingfeng Huang, Zexin Fu, Qinhao Gu, Ji Wang, Yi Sun, Yong He, Sufan Wu, Xiaojie Hu, Chengrui Guo
Summary: This study conducted a bibliometric analysis of the MPNST literature from 2000 to 2022 to identify historical trends and publication patterns. The results showed a continuous increase in the number of publications on MPNST since 2000, with the USA, Japan, and China being the most productive countries. The journal Modern Pathology had the highest number of MPNST publications, while articles in the Cancer Research journal were most frequently cited. The University of Texas MD Anderson Cancer Center may be a valuable collaborator. Recent research trends in MPNST focused on tumorigenesis, clinical management, and predictive biomarkers.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biology
Yihui Gu, Zhichao Wang, Chengjiang Wei, Yuehua Li, Wei Feng, Wei Wang, Meiqi Chang, Yu Chen, Qingfeng Li
Summary: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with poor prognosis, requiring new therapeutic strategies. This study evaluates the efficiency, safety, and mechanisms of using NIR-III without photothermal agents in treating MPNSTs. Results show varying efficacy of NIR-III photothermal treatment, influenced by endoplasmic reticulum stress responses, but ultimately achieving the expected antineoplastic effect after adjustments.
Article
Oncology
Juana Ferna, Edgar Creus-Bachiller, Xiaohu Zhang, Maria Martinez-Iniesta, Sara Ortega-Bertran, Rajarshi Guha, Craig J. Thomas, Margaret R. Wallace, Cleofe Romagosa, Lourdes Salazar-Huayna, Karlyne M. Reilly, Jaishri O. Blakely, Jordi Serra-Musach, Miguel Angel Pujana, Eduard Serra, Alberto Villanueva, Marc Ferrer, Conxi Lazaro
Summary: Malignant peripheral nerve sheath tumors (MPNST) are a leading cause of mortality. High-throughput screening identified several synergistic compound combinations, including MK-1775 with Doxorubicin, which showed significant anti-tumor effects in MPNST.
MOLECULAR CANCER THERAPEUTICS
(2022)
Letter
Oncology
John Lennon Silva Cunha, Saygo Tomo, Ederson Kerlakian de Paiva Gomes Fernandes, Margarite Maria Delmondes Freitas, Oslei Paes de Almeida, Bruno Augusto Benevenuto de Andrade, Ciro Dantas Soares, Ricardo Luiz Cavalcanti de Albuquerque-Junior
Summary: This study reports a rare case of intraosseous MPNST in a 28-year-old male without neurofibromatosis type 1, discovered as an incidental finding on imaging exam. After wide surgical resection, the patient remained with no evidence of recurrence or metastatic disease during a three-year follow-up.
Article
Oncology
Esmail Al-Ezzi, Mrinal Gounder, Geoffrey Watson, Alessandro Mazzocca, Sandra P. D'Angelo, Julie Bravetti, Hongwei Wang, Albiruni Abdul Razak, Bruno Vincenzi
Summary: This study reports nine cases of MPNST treated with selinexor, showing tumor stabilization or regression as a result.
Article
Genetics & Heredity
Jose Marcos Moreno-Cabrera, Jesus del Valle, Lidia Feliubadalo, Marta Pineda, Sara Gonzalez, Olga Campos, Raquel Cuesta, Joan Brunet, Eduard Serra, Gabriel Capella, Bernat Gel, Conxi Lazaro
Summary: This study evaluated a next-generation sequencing-based CNV detection tool (DECoN) as a first-tier screening for genetic diagnostics in hereditary cancer. The results showed that DECoN could detect more CNVs while reducing turnaround time and costs.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Nuria Catasus, Belen Garcia, Ivan Galvan-Femenia, Adria Plana, Alejandro Negro, Inma Rosas, Andrea Ros, Emilio Amilibia, Juan Luis Becerra, Cristina Hostalot, Francesc Rocaribas, Isabel Bielsa, Conxi Lazaro Garcia, Rafael de Cid, Eduard Serra, Ignacio Blanco, Elisabeth Castellanos
Summary: The UK NF2 GSS was validated in a Spanish NF2 cohort, with significant variability in phenotypes. Modifications to the GSS, known as Functional Genetic Severity Score, may improve classification for mosaic and mild/moderate phenotype patients once validated in other cohorts.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Oncology
Madeline Niederkorn, Chiharu Ishikawa, Kathleen M. Hueneman, James Bartram, Emily Stepanchick, Joshua R. Bennett, Ashley E. Culver-Cochran, Lyndsey C. Bolanos, Emma Uible, Kwangmin Choi, Mark Wunderlich, John P. Perentesis, Timothy M. Chlon, Marie-Dominique Filippi, Daniel T. Starczynowski
Summary: USP15 is overexpressed in AML, correlating with KEAP1 protein and NRF2 suppression. Inhibition of USP15 leads to activation of NRF2 and impaired AML cell function. Targeting USP15 catalytic function may selectively impair leukemic progenitor cells while sparing normal hematopoiesis.
Article
Genetics & Heredity
Arkadiusz Piotrowski, Magdalena Koczkowska, Andrzej B. Poplawski, Rafal Bartoszewski, Jaroslaw Kroliczewski, Alina Mieczkowska, Alicia Gomes, Michael R. Crowley, David K. Crossman, Yunjia Chen, Ping Lao, Eduard Serra, Meritxell C. Llach, Elisabeth Castellanos, Ludwine M. Messiaen
Summary: Constitutional pathogenic variants in genes LZTR1 or SMARCB1 were identified in a high percentage of familial and sporadic schwannomatosis cases, with additional novel variants and potential predisposing candidate genes revealed through extensive sequencing.
Article
Genetics & Heredity
Belen Garcia, Nuria Catasus, Andrea Ros, Inma Rosas, Alejandro Negro, Mercedes Guerrero-Murillo, Ana Maria Valero, Anna Duat-Rodriguez, Juan Luis Becerra, Sandra Bonache, Conxi Lazaro Garcia, Carmina Comas, Isabel Bielsa, Eduard Serra, Concepcion Hernandez-Chico, Yolanda Martin, Elisabeth Castellanos, Ignacio Blanco
Summary: This study suggests that offspring of male patients with NF1 may have an increased risk of experiencing de novo NF1 pathogenic variants, which has important implications for NF1 genetic counseling, family planning, and NF1 genetic testing.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Oncology
Shailaja Hegde, Anjelika Gasilina, Mark Wunderlich, Yuan Lin, Marcel Buchholzer, Oliver H. F. Krumbach, Mohammad Akbarzadeh, Mohammad Reza Ahmadian, William Seibel, Yi Zheng, John P. Perentesis, Benjamin E. Mizukawa, Lisa Privette Vinnedge, Jose A. Cancelas, Nicolas N. Nassar
Summary: The small-molecule inhibitor IODVA1 targeting VAV3 effectively inhibits RAC activation and signaling, leading to increased pro-apoptotic activity in BCR-ABL1-transformed cells. In difficult-to-treat pediatric Ph+ and TKI-resistant Ph+ B-ALL patient-derived xenograft models, IODVA1 outperforms dasatinib or ponatinib and provides a more durable response after treatment withdrawal.
Editorial Material
Oncology
Alexandra Power-Hays, Christopher E. Dandoy, Angela Lorts, John P. Perentesis, Ndidi Unaka, Russell E. Ware, Patrick T. McGann
PEDIATRIC BLOOD & CANCER
(2022)
Article
Cell Biology
Laura Barreyro, Avery M. Sampson, Chiharu Ishikawa, Kathleen M. Hueneman, Kwangmin Choi, Mario A. Pujato, Somchai Chutipongtanate, Michael Wyder, Wendy D. Haffey, Eric O'Brien, Mark Wunderlich, Vighnesh Ramesh, Ellen M. Kolb, Cem Meydan, Yaseswini Neelamraju, Lyndsey C. Bolanos, Susanne Christie, Molly A. Smith, Madeline Niederkorn, Tomoya Muto, Santosh Kesari, Francine E. Garrett-Bakelman, Boris Bartholdy, Britta Will, Matthew T. Weirauch, James C. Mulloy, Zartash Gul, Stephen Medlin, Rhett A. Kovall, Ari M. Melnick, John P. Perentesis, Kenneth D. Greis, Elmar Nurmemmedov, William L. Seibel, Daniel T. Starczynowski
Summary: This study found that dysregulation of immune signaling pathways is associated with oncogenic immune signaling states in acute myeloid leukemia (AML) hematopoietic stem and progenitor cells. Inhibition of the ubiquitin-conjugating enzyme UBE2N disrupted oncogenic immune signaling and promoted cell death in AML cells while sparing normal cells. These findings highlight the potential of interfering with UBE2N function as a therapeutic strategy for AML.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Miriam Magallon-Lorenz, Ernest Terribas, Sara Ortega-Bertran, Edgar Creus-Bachiller, Marco Fernandez, Gerard Requena, Inma Rosas, Helena Mazuelas, Itziar Uriarte-Arrazola, Alex Negro, Tereza Lausova, Elisabeth Castellanos, Ignacio Blanco, George DeVries, Hiroyuki Kawashima, Eric Legius, Hilde Brems, Viktor Mautner, Lan Kluwe, Nancy Ratner, Margaret Wallace, Juana Fernandez-Rodriguez, Conxi Lazaro, Jonathan A. Fletcher, David Reuss, Meritxell Carrio, Bernat Gel, Eduard Serra
Summary: This article presents the genomic characterization of 9 widely used human MPNST cell lines, providing valuable resources for translational research. NF1-related cell lines exhibited characteristics similar to primary MPNSTs, while sporadic cell lines showed different inactivation patterns of tumor suppressor genes and mutations. The re-classification of cell lines as melanomas and other sarcomas demonstrated different responses to drug treatment. Deep genomic analysis, methylome-based classification, and cell-identity marker expression challenged the identity of common MPNST cell lines, highlighting the need for revisions in MPNST diagnosis.
Article
Dermatology
Verena Staedtke, Piotr Topilko, Lu Q. Le, Kevin Grimes, David A. Largaespada, Ross L. Cagan, Matthew R. Steensma, Anat Stemmer-Rachamimov, Jaishri O. Blakeley, Steven D. Rhodes, Ina Ly, Carlos G. Romo, Sang Y. Lee, Eduard Serra
Summary: Neurofibromatosis type 1 (NF1) is caused by a nonfunctional NF1 tumor suppressor gene, resulting in the development of cutaneous neurofibromas (cNFs). Incomplete understanding of cNF pathophysiology and limitations in experimental modeling have hindered the development of cNF treatment. Recent advances in preclinical in vitro and in vivo modeling provide unprecedented opportunities for therapeutic discovery and improving our understanding of cNF biology.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Chunhui Jiang, Renee M. Mckay, Sang Y. Lee, Carlos G. Romo, Jaishri O. Blakeley, Muzlifah Haniffa, Eduard Serra, Matthew R. Steensma, David Largaespada, Lu Q. Le
Summary: Neurofibromatosis type 1 is a common genetic disorder that predisposes patients to develop tumors. Cutaneous neurofibromas significantly impact patients' quality of life due to their unaesthetic appearance and physical discomfort. Understanding the factors involved in the heterogeneity of cNF can help develop personalized treatment regimens.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Jaishri O. Blakeley, Lu Q. Le, Sang Y. Lee, Ina Ly, Steven D. Rhodes, Carlos G. Romo, Kavita Y. Sarin, Verena Staedtke, Matthew R. Steensma, Pierre Wolkenstein
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Youjin Na, Ashley Hall, Yanan Yu, Liang Hu, Kwangmin Choi, Jake A. Burgard, Sara Szabo, Gang Huang, Nancy Ratner, Jianqiang Wu
Summary: Neurofibromatosis type 1 (NF1) patients are prone to develop plexiform neurofibromas (PNFs), and all three endoplasmic reticulum (ER) stress response pathways are activated in PNFs. Inhibition of protein kinase RNA [PKR]-like ER kinase (PERK) can reduce the number of neurofibroma-spheres and tumor-like lesions in mouse models. Deletion of PERK in Schwann cells (SCs) and Schwann cell precursors (SCPs) leads to reduced tumor size, number, and increased survival in a PNF mouse model. Targeting proteostasis could be a potential therapy for PNFs.
Article
Biochemical Research Methods
Helena Mazuelas, Itziar Uriarte-Arrazola, Juana Fernandez-Rodriguez, Miriam Magallon-Lorenz, Alberto Villanueva, Conxi Lazaro, Bernat Gel, Eduard Serra, Meritxell Carrio
Summary: This study generated neurofibromaspheres by differentiating NF1(-/-) Schwann cells from induced pluripotent stem cells and combining them with neurofibroma primary fibroblasts. Neurofibroma-like tumors were developed when these neurofibromaspheres were engrafted in the sciatic nerve of nude mice. This model provides a versatile platform for drug screening and the study of neurofibroma biology.
Article
Oncology
Edgar Creus-Bachiller, Juana Fernandez-Rodriguez, Miriam Magallon-Lorenz, Sara Ortega-Bertran, Susana Navas-Rutete, Cleofe Romagosa, Tulio M. Silva, Maria Pane, Anna Estival, Diana Perez Sidelnikova, Mireia Morell, Helena Mazuelas, Meritxell Carrio, Tereza Lausova, David Reuss, Bernat Gel, Alberto Villanueva, Eduard Serra, Conxi Lazaro
Summary: This study presents an extension of an MPNST precision medicine platform, incorporating new PDOXs and cell lines that accurately recapitulate the characteristics of primary tumors. The diverse tumor identities and associated genomic alterations impact treatment responses, highlighting the importance of correct preclinical information for guiding MPNST clinical trials.
MOLECULAR ONCOLOGY
(2023)