Article
Medicine, Research & Experimental
Quan Zhou, S. Nynke van den Berg, L. Eben Rosenthal, Michael Iv, Michael Zhang, C. M. Johana Vega Leonel, Shannon Walters, Naoki Nishio, Monica Granucci, Roan Raymundo, Grace Yi, Hannes Vogel, Romain Cayrol, Yu-Jin Lee, Guolan Lu, Marisa Hom, Wenying Kang, Melanie Hayden Gephart, Larry Recht, Seema Nagpal, Reena Thomas, Chirag Patel, A. Gerald Grant, Gordon Li
Summary: The study evaluated the safety and efficacy of using panitumumab-IRDye800 as an imaging agent for high-grade gliomas, showing that it provided good tumor contrast at both doses. The 100 mg dose was able to detect smaller tumor fragments, making it more suitable for intraoperative imaging.
Article
Oncology
Emeline Tabouret, Michel Fabbro, Didier Autran, Khe Hoang-Xuan, Luc Taillandier, Francois Ducray, Maryline Barrie, Marc Sanson, Christine Kerr, Stephanie Cartalat-Carel, Anderson Loundou, Remy Guillevin, Karima Mokhtari, Dominique Figarella-Branger, Jean-Yves Delattre, Olivier Chinot
Summary: Combination treatment with temozolomide and BCNU shows promising response and survival rates for patients with unresectable anaplastic gliomas, but its use is limited by toxicity. Different factors, such as IDH mutation and MGMT promoter methylation, may influence the prognosis for these patients.
Article
Oncology
Pierre Leblond, Emmanuelle Tresch-Bruneel, Alicia Probst, Nadege Neant, Caroline Solas, Arthur Sterin, Thomas Boulanger, Isabelle Aerts, Cecile Faure-Conter, Anne-Isabelle Bertozzi, Pascal Chastagner, Natacha Entz-Werle, Emilie De Carli, Marie-Cecile Le Deley, Gauthier Bouche, Nicolas Andre
Summary: This study tested the repurposing of two non-anticancer drugs to provide less toxic therapeutic options for children with gliomas. The recommended phase II dose of fluvastatin in combination with celecoxib for children with gliomas is 6mg/kg/day, with a fixed daily dose of celecoxib depending on weight. This combination may be explored as a maintenance treatment in low-grade glioma patients to delay tumor recurrence.
Review
Clinical Neurology
James L. Ross, Jose Velazquez Vega, Ashley Plant, Tobey J. MacDonald, Oren J. Becher, Dolores Hambardzumyan
Summary: Significant progress has been made in elucidating the origin and genomic landscape of childhood high-grade brain tumors over the past decade. However, clinical trials for children with gliomas have historically been ineffective due to a lack of consideration for the fundamental biological differences between pediatric and adult tumors. Little is known about the dynamic tumor immune microenvironment in pediatric high-grade gliomas despite expanded knowledge on cellular mechanisms driving tumor progression.
Article
Oncology
Danielle Golub, Daniel G. Lynch, Peter C. Pan, Benjamin Liechty, Cheyanne Slocum, Tejus Bale, David J. Pisapia, Rupa Juthani
Summary: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a rare tumor that can mimic high-grade glioma in histologic and molecular features. This study describes a case of indolent neuroepithelial neoplasm in an adult female patient and compares it with adult glioma patients harboring FGFR3-TACC3 fusion gene. The presence of FGFR3-TACC3 fusion gene and other high-grade features should raise concern for a more malignant precursor lesion in the diagnosis of PLNTY.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Jason Fangusaro, Arzu Onar-Thomas, Tina Young Poussaint, Shengjie Wu, Azra H. Ligon, Neal Lindeman, Olivia Campagne, Anu Banerjee, Sridharan Gururangan, Lindsay B. Kilburn, Stewart Goldman, Ibrahim Qaddoumi, Patricia Baxter, Gilbert Vezina, Corey Bregman, Zoltan Patay, Jeremy Y. Jones, Clinton F. Stewart, Michael J. Fisher, Laurence Austin Doyle, Malcolm Smith, Ira J. Dunkel, Maryam Fouladi
Summary: This study presented the results of treating children with recurrent/progressive OPHGs using selumetinib in a PBTC phase II trial. The treatment resulted in partial responses in 24% of patients, stable disease in 56%, and disease progression in 20%, with a median number of 26 treatment courses. The two-year PFS was 78%, and evaluation of visual acuity showed improvement and stability in a portion of patients.
Article
Oncology
Christelle Dufour, Stephanie Foulon, Anne Geoffray, Julien Masliah-Planchon, Dominique Figarella-Branger, Valerie Bernier-Chastagner, Laetitia Padovani, Lea Guerrini-Rousseau, Cecile Faure-Conter, Celine Icher, Anne-Isabelle Bertozzi, Pierre Leblond, Tasnime Akbaraly, Franck Bourdeaut, Nicolas Andre, Celine Chappe, Pascale Schneider, Emilie De Carli, Pascal Chastagner, Claire Berger, Julien Lejeune, Christine Soler, Natacha Entz-Werle, Marie-Bernadette Delisle
Summary: This study assessed the efficacy of a treatment regimen involving high-dose chemotherapy and conventional radiotherapy for children with newly diagnosed high-risk medulloblastoma. The results showed 3 and 5-year progression-free survival rates of 78% and 76% respectively, with good tolerability of the treatment regimen.
Article
Oncology
William G. Breen, Ryan S. Youland, Sharmila Giri, Sawyer B. Jacobson, Deanna H. Pafundi, Paul D. Brown, Christopher H. Hunt, Anita Mahajan, Michael W. Ruff, Sani H. Kizilbash, Joon H. Uhm, David M. Routman, Jamecca E. Jones, Debra H. Brinkmann, Nadia N. Laack
Summary: This study investigated the effect of F-18-DOPA PET and MRI-guided re-irradiation on PFS in recurrent high-grade glioma, and the results suggest that this approach may improve survival.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Article
Pediatrics
Eric M. Thompson, Daniel Landi, Michael C. Brown, Henry S. Friedman, Roger McLendon, James E. Herndon II, Evan Buckley, Dani P. Bolognesi, Eric Lipp, Kristin Schroeder, Oren J. Becher, Allan H. Friedman, Zachary McKay, Ashley Walter, Stevie Threatt, Denise Jaggers, Annick Desjardins, Matthias Gromeier, Darell Bigner, David M. Ashley
Summary: This study aimed to evaluate the safety and overall survival of lerapolturev, a viral immunotherapy, when administered as a single dose intracerebrally in children and young people with recurrent paediatric high-grade glioma. The results showed that lerapolturev demonstrated promising potential in the treatment of recurrent paediatric high-grade glioma within a tolerable range.
LANCET CHILD & ADOLESCENT HEALTH
(2023)
Article
Medicine, General & Internal
Anna Pieczynska, Ewa Zasadzka, Agnieszka Pilarska, Danuta Procyk, Krystyna Adamska, Katarzyna Hojan
Summary: This study aimed to investigate the effects of augmented-reality-based rehabilitation exercises on patients with high-grade glioma (HGG). The results showed that there were no significant changes in the exercise group, but the control group experienced a significant decrease in handgrip strength and attention. No significant changes were observed in quality of life (QoL), fatigue, brain derived neurotrophic factor (BDNF), or S100 protein levels in either group. Therefore, augmented-reality-based exercise may help prevent muscle strength and attention loss in HGG patients during radiation therapy.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Oncology
Jamie-Lee Pitcher, Naomi Alexander, Panimaya Jeffreena Miranda, Terrance G. G. Johns
Summary: This review focuses on the unique biology of ErbB4 in the brain and highlights brain cancer research findings. However, there is little known about the signaling activity of ErbB4 in brain cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Pierina Navarria, Federico Pessina, Elena Clerici, Luisa Bellu, Ciro Franzese, Andrea Franzini, Matteo Simonelli, Lorenzo Bello, Armando Santoro, Letterio Salvatore Politi, Giuseppe Roberto D'agostino, Alessandra Casarotti, Bethania Fernandes, Valter Torri, Marta Scorsetti
Summary: This is a single arm prospective phase II study evaluating the efficacy and toxicity of re-irradiation in recurrent high grade glioma. The results showed that re-irradiation is a safe and feasible treatment option, with better outcomes in younger patients and those with grade 3 IDH mutated gliomas.
RADIOTHERAPY AND ONCOLOGY
(2022)
Article
Oncology
Nicoletta Colombo, Federica Tomao, Pierluigi Benedetti Panici, Maria Ornella Nicoletto, Germana Tognon, Alessandra Bologna, Andrea Alberto Lissoni, Andrea DeCensi, Mariateresa Lapresa, Rosanna Mancari, Innocenza Palaia, Giulia Tasca, Francesca Tettamanzi, Maria Francesca Alvisi, Eliana Rulli, Davide Poli, Luciano Carlucci, Valter Torri, Roldano Fossati, Elena Biagioli
Summary: The combination of cediranib and olaparib did not improve the progression-free survival (PFS) compared to chemotherapy in heavily pretreated platinum-resistant ovarian cancer patients. However, this oral doublet is still an effective option for this difficult-to-treat population.
GYNECOLOGIC ONCOLOGY
(2022)
Review
Oncology
Dennis S. Metselaar, Aimee du Chatinier, Iris Stuiver, Gertjan J. L. Kaspers, Esther Hulleman
Summary: Pediatric high-grade gliomas are fatal brain tumors in children, characterized by mutations in histone 3 genes and therapy-resistant stem cell-like phenotype. Standard treatments like surgery and radiation therapy offer limited success, but new opportunities lie in radiosensitizers for improved outcomes.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Marc-Antoine Da-Veiga, Bernard Rogister, Arnaud Lombard, Virginie Neirinckx, Caroline Piette
Summary: Pediatric high-grade glioma (pHGG) has a poor prognosis, especially in younger patients. The highly malignant glioma stem cells (GSCs) remain poorly investigated in pediatric cases, despite being well described in adult brain tumors. Understanding the role of GSCs in pediatric tumors could lead to targeted treatments for better outcomes.
Article
Cell Biology
Deanna M. Patmore, Amir Jassim, Erica Nathan, Reuben J. Gilbertson, Daniel Tahan, Nadin Hoffmann, Yiai Tong, Kyle S. Smith, Thirumala-Devi Kanneganti, Hiromichi Suzuki, Michael D. Taylor, Paul Northcott, Richard J. Gilbertson
DEVELOPMENTAL CELL
(2020)
Article
Cell Biology
Frank Szulzewsky, Sonali Arora, Pia Hoellerbauer, Claire King, Erica Nathan, Marina Chan, Patrick J. Cimino, Tatsuya Ozawa, Daisuke Kawauchi, Kristian W. Pajtler, Richard J. Gilbertson, Patrick J. Paddison, Valeri Vasioukhin, Taranjit S. Gujral, Eric C. Holland
GENES & DEVELOPMENT
(2020)
Review
Developmental Biology
Silvia Marino, Richard J. Gilbertson
Summary: Brain tumors are the most common solid neoplasms in children, representing one quarter of all childhood cancers. Understanding basic developmental mechanisms has greatly contributed to our knowledge of the pathogenesis of these tumors, influencing clinical decisions in treating children with these diseases.
Article
Oncology
Amar Gajjar, Giles W. Robinson, Kyle S. Smith, Tong Lin, Thomas E. Merchant, Murali Chintagumpala, Anita Mahajan, Jack Su, Eric Bouffet, Ute Bartels, Tal Schechter, Tim Hassall, Thomas Robertson, Wayne Nicholls, Sridharan Gururangan, Kristin Schroeder, Michael Sullivan, Greg Wheeler, Jordan R. Hansford, Stewart J. Kellie, Geoffrey McCowage, Richard Cohn, Michael J. Fisher, Matthew J. Krasin, Clinton F. Stewart, Alberto Broniscer, Ivo Buchhalter, Ruth G. Tatevossian, Brent A. Orr, Geoff Neale, Paul Klimo, Frederick Boop, Ashok Srinivasan, Stefan M. Pfister, Richard J. Gilbertson, Arzu Onar-Thomas, David W. Ellison, Paul A. Northcott
Summary: The study identified new risk stratification for medulloblastoma treatment through molecular classification and risk factor analysis, finding differences in PFS among patients with different genotypes and subtypes.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Editorial Material
Oncology
Sam Behjati, Richard J. Gilbertson, Stefan M. Pfister
Summary: The main differences between childhood tumors and adult cancers lie in the cellular origin and development stages, which may offer insights for researching and treating childhood cancer.
Article
Oncology
Robert Kupp, Lisa Ruff, Sabrina Terranova, Erica Nathan, Stephane Ballereau, Rory Stark, Chandra Sekhar Reddy Chilamakuri, Nadin Hoffmann, Katherine Wickham-Rahrmann, Marcus Widdess, Amir Arabzade, Yanhua Zhao, Srinidhi Varadharajan, Tuyu Zheng, Mohankumar Murugesan, Stefan M. Pfister, Daisuke Kawauch, Kristian W. Pajtler, Benjamin Deneen, Stephen C. Mack, Katherine E. Masih, Berkley E. Gryder, Javed Khan, Richard J. Gilbertson
Summary: The study reveals that ZFTA fusion proteins drive the development of supratentorial ependymoma and unravels their transformation mechanism, providing clues for therapy. By investigating deletion-mutant genes, the study identifies a tripartite transformation mechanism of ZFTA-containing fusions, including nuclear translocation, chromatin binding, and recruitment of chromatin modifier complexes.
Article
Oncology
Tuyu Zheng, David R. Ghasemi, Konstantin Okonechnikov, Andrey Korshunov, Martin Sill, Kendra K. Maass, Patricia Benites Goncalves da Silva, Marina Ryzhova, Johannes Gojo, Damian Stichel, Amir Arabzade, Robert Kupp, Julia Benzel, Shinichiro Taya, Toma Adachi, Ryo Shiraishi, Nicolas U. Gerber, Dominik Sturm, Jonas Ecker, Philipp Sievers, Florian Selt, Rebecca Chapman, Christine Haberler, Dominique Figarella-Branger, Guido Reifenberger, Gudrun Fleischhack, Stefan Rutkowski, Andrew M. Donson, Vijay Ramaswamy, David Capper, David W. Ellison, Christel C. Herold-Mende, Ulrich Schueller, Sebastian Brandner, Pablo Hernaiz Driever, Johan M. Kros, Matija Snuderl, Till Milde, Richard G. Grundy, Mikio Hoshino, Stephen C. Mack, Richard J. Gilbertson, David T. W. Jones, Marcel Kool, Andreas von Deimling, Stefan M. Pfister, Felix Sahm, Daisuke Kawauchi, Kristian W. Pajtler
Summary: Supratentorial ependymomas can be categorized into tumors with ZFTA-RELA or YAP1 fusions, fusion-negative subependymomas, and other tumors that cannot be classified. ZFTA acts as a partner gene in oncogenic fusions with various histologic features, with GLI2 identified as a key regulator of tumorigenesis in these tumors. Targeting GLI2 with arsenic trioxide shows potential therapeutic benefits for ZFTA fusion-positive tumors.
Article
Oncology
Amir Arabzade, Yanhua Zhao, Srinidhi Varadharajan, Hsiao-Chi Chen, Selin Jessa, Bryan Rivas, Austin J. Stuckert, Minerva Solis, Alisha Kardian, Dana Tlais, Brian J. Golbourn, Ann-Catherine J. Stanton, Yuen San Chan, Calla Olson, Kristen L. Karlin, Kathleen Kong, Robert Kupp, Baoli Hu, Sarah G. Injac, Madeline Ngo, Peter R. Wang, Luz A. De Leon, Felix Sahm, Daisuke Kawauchi, Stefan M. Pfister, Charles Y. Lin, H. Courtney Hodges, Irtisha Singh, Thomas F. Westbrook, Murali M. Chintagumpala, Susan M. Blaney, Donald W. Parsons, Kristian W. Pajtler, Sameer Agnihotri, Richard J. Gilbertson, Joanna Yi, Nada Jabado, Claudia L. Kleinman, Kelsey C. Bertrand, Benjamin Deneen, Stephen C. Mack
Summary: The study reveals the critical role of ZR(fus) in supratentorial ependymomas by activating the NF kappa B pathway and recruiting transcriptional coactivators to promote gene expression. Its target genes are often involved in developmental programs and tumor networks, providing insights for potential therapeutic strategies.
Article
Oncology
Anthony P. Y. Liu, Kyle S. Smith, Rahul Kumar, Leena Paul, Laure Bihannic, Tong Lin, Kendra K. Maass, Kristian W. Pajtler, Murali Chintagumpala, Jack M. Su, Eric Bouffet, Michael J. Fisher, Sridharan Gururangan, Richard Cohn, Tim Hassall, Jordan R. Hansford, Paul Klimo, Frederick A. Boop, Clinton F. Stewart, Julie H. Harreld, Thomas E. Merchant, Ruth G. Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery M. Klco, Brent A. Orr, David W. Ellison, Richard J. Gilbertson, Arzu Onar-Thomas, Amar Gajjar, Giles W. Robinson, Paul A. Northcott
Summary: The study demonstrates the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of measurable residual disease (MRD) in children with medulloblastoma. Detection of MRD, particularly in patients with persistent MRD, is associated with a higher risk of disease progression. Early detection of MRD using liquid biopsies may aid in monitoring disease progression and treatment efficacy in medulloblastoma patients.
Article
Cell Biology
Pooja Panwalkar, Benita Tamrazi, Derek Dang, Chan Chung, Stefan Sweha, Siva Kumar Natarajan, Matthew Pun, Jill Bayliss, Martin P. Ogrodzinski, Drew Pratt, Brendan Mullan, Debra Hawes, Fusheng Yang, Chao Lu, Benjamin R. Sabari, Abhinav Achreja, Jin Heon, Olamide Animasahun, Marcin Cieslik, Christopher Dunham, Stephen Yip, Juliette Hukin, Joanna J. Phillips, Miriam Bornhorst, Andrea M. Griesinger, Andrew M. Donson, Nicholas K. Foreman, Hugh J. L. Garton, Jason Heth, Karin Muraszko, Javad Nazarian, Carl Koschmann, Li Jiang, Mariella G. Filbin, Deepak Nagrath, Marcel Kool, Andrey Korshunov, Stefan M. Pfister, Richard J. Gilbertson, C. David Allis, Arul M. Chinnaiyan, Sophia Y. Lunt, Stefan Bluml, Alexander R. Judkins, Sriram Venneti
Summary: Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and poor prognoses compared to group B ependymomas (PFBs). PFAs exhibit enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism, with high expression of glycolytic genes associated with a poor outcome. These tumors also show high EZHIP expression linked to a dismal prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Repurposing the antidiabetic drug metformin has shown therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts by targeting integrated metabolic/epigenetic pathways.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Sreenath Nair, Abigail Davis, Olivia Campagne, John D. Schuetz, Clinton F. Stewart
Summary: This study successfully determined the concentration of IWR-1-endo in murine plasma and brain microdialysate using LC-MS/MS. pH adjustment to 1.5 improved the stability of IWR-1-endo in the samples before storage and processing.
Article
Genetics & Heredity
Eric P. Rahrmann, David Shorthouse, Amir Jassim, Linda P. Hu, Mariaestela Ortiz, Betania Mahler-Araujo, Peter Vogel, Marta Paez-Ribes, Atefeh Fatemi, Gregory J. Hannon, Radhika Iyer, Jay A. Blundon, Filipe C. Lourenco, Jonathan Kay, Rosalynn M. Nazarian, Benjamin A. Hall, Stanislav S. Zakharenko, Douglas J. Winton, Liqin Zhu, Richard J. Gilbertson
Summary: The ion channel NALCN has been identified as a key regulator of cancer metastasis and nonmalignant cell dissemination, even in the absence of oncogenic mutations, allowing normal structures to form at secondary sites. This finding uncovers a potential new target for antimetastatic therapies.
Article
Multidisciplinary Sciences
Zaili Luo, Mingyang Xia, Wei Shi, Chuntao Zhao, Jiajia Wang, Dazhuan Xin, Xinran Dong, Yu Xiong, Feng Zhang, Kalen Berry, Sean Ogurek, Xuezhao Liu, Rohit Rao, Rui Xing, Lai Man Natalie Wu, Siying Cui, Lingli Xu, Yifeng Lin, Wenkun Ma, Shuaiwei Tian, Qi Xie, Li Zhang, Mei Xin, Xiaotao Wang, Feng Yue, Haizi Zheng, Yaping Liu, Charles B. Stevenson, Peter de Blank, John P. Perentesis, Richard J. Gilbertson, Hao Li, Jie Ma, Wenhao Zhou, Michael D. Taylor, Q. Richard Lu
Summary: In this study, single-cell profiling of human fetal cerebella was performed to investigate the cellular states and regulatory networks in medulloblastomas (MBs). The researchers found a unique transitional cerebellar progenitor population enriched in aggressive MB subgroups and identified transcriptional determinants HNRNPH1 and SOX11 that are correlated with prognosis in group 3 MBs. Genomic analysis revealed long-range chromatin loops connecting HNRNPH1/SOX11-targeted super-enhancers to regulatory elements of the oncogenic driver MYC in group 3 MBs. Targeting the transitional progenitor regulators inhibited MYC expression and MB growth. This study provides new insights into the cellular and molecular characteristics of MBs, which may have implications for disease prognosis and potential therapeutic strategies.
Review
Oncology
Amir Jassim, Eric P. Rahrmann, Ben D. Simons, Richard J. Gilbertson
Summary: Understanding the combination of cell intrinsic and extrinsic factors in initiating transformation is important for cancer prevention, detection, and early treatment. This review outlines current theories on cancer origins and the underlying determinants of cancer risk. While cancer has been a leading cause of death for decades, controversy remains regarding the transformation of tissues, hindering effective prevention and early intervention. By understanding the complex interplay of cell intrinsic and extrinsic factors, effective strategies for preventing, detecting, and stopping cancer before it becomes incurable can be discovered.
NATURE REVIEWS CANCER
(2023)
Article
Biochemistry & Molecular Biology
Kieran Foley, David Shorthouse, Eric Rahrmann, Lizhe Zhuang, Ginny Devonshire, Rebecca C. OCCAMS Consortium, Rebecca C. Fitzgerald, Benjamin A. Hall
Summary: Metastasis in oesophageal adenocarcinoma (OAC) is a crucial factor affecting survival. Radiological staging is commonly used to assess metastases, but its accuracy is limited. This study analyzed lymph node metastases and identified new roles of genes SMAD4 and KCNQ3 in metastasis. The findings suggest that both genes could serve as novel biomarkers for metastatic risk and offer potential new targets for drug treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)