Review
Oncology
Vincenzo Di Nunno, Enrico Franceschi, Alicia Tosoni, Lidia Gatto, Raffaele Lodi, Stefania Bartolini, Alba Ariela Brandes
Summary: Glioblastoma patients face a lack of systemic agents with clinical efficacy, emphasizing the need for novel therapeutic approaches. However, the increasing availability of novel compounds and better biological knowledge of the disease offer hope for more promising clinical trials. Focus on novel trial designs and emerging treatment strategies is essential for moving forward in the management of glioblastoma.
Article
Oncology
Mehrshad Sadria, Deokhwa Seo, Anita T. Layton
Summary: AMPK plays a complex and contradictory role in cancer. Before the onset of cancer, AMPK acts as a tumor suppressor; however, after the onset of cancer, the role of AMPK varies depending on cell type or state.
Article
Immunology
Hang Ji, Zhihui Liu, Fang Wang, Haogeng Sun, Nan Wang, Yi Liu, Shaoshan Hu, Chao You
Summary: This study aims to construct a Macrophage-Related Gene Prognostic Index (MRGPI) for glioblastoma (GBM) and explore the underlying molecular, metabolic, and immunological features. The MRGPI was found to be an independent risk factor and correlated with macrophage activation. The study provides insights into the prognosis, metabolism, and immune features of GBM, and facilitates personalized application of immune checkpoint inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Denise Sighel, Michela Notarangelo, Shintaro Aibara, Angela Re, Gianluca Ricci, Marianna Guida, Alessia Soldano, Valentina Adami, Chiara Ambrosini, Francesca Broso, Emanuele Filiberto Rosatti, Sara Longhi, Mariachiara Buccarelli, Quintino G. D'Alessandris, Stefano Giannetti, Simone Pacioni, Lucia Ricci-Vitiani, Joanna Rorbach, Roberto Pallini, Sandrine Roulland, Alexey Amunts, Ines Mancini, Angelika Modelska, Alessandro Quattrone
Summary: This study suggests that targeting mitochondrial translation could be a potential therapeutic strategy to suppress GSC growth in GBM. The bacterial antibiotic quinupristin/dalfopristin (Q/D) was found to effectively inhibit GSC growth by binding to the large mitoribosomal subunit, inhibiting mitochondrial protein synthesis, and disrupting OXPHOS complexes.
Review
Cell Biology
Huidong Liu, Ye-Guang Chen
Summary: TGF-beta signaling plays a critical role in metabolism and is closely related to the progression of various diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Zhiwei Xue, Jiwei Wang, Zide Wang, Junzhi Liu, Jiangli Zhao, Xuchen Liu, Yan Zhang, Guowei Liu, Zhimin Zhao, Wenjie Li, Qing Zhang, Xingang Li, Bin Huang, Xinyu Wang
Summary: The overexpression of SLC25A32 in human glioblastoma (GBM) is associated with the malignancy and poor prognosis. Experimental results showed that SLC25A32 promotes the proliferation and invasion of GBM cells, mainly through the activation of the PI3K-AKT-mTOR signaling pathway. Therefore, SLC25A32 can serve as an independent prognostic factor in GBM patients, providing a new target for the comprehensive treatment of GBM.
Review
Biochemistry & Molecular Biology
Zeyu Wang, Hao Zhang, Shengchao Xu, Zhixiong Liu, Quan Cheng
Summary: Glioblastoma stem cells pose a challenge in therapy resistance, with different subtypes or metabolic patterns potentially leading to varying sensitivity. Involvement of neural stem cells in tumor resistance to treatments is also a possibility.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Review
Pharmacology & Pharmacy
Meng Zhang, Qian Lei, Xiaobo Huang, Yi Wang
Summary: This study reviews the role and mechanism of ferroptosis in glioblastoma, as well as the research status and progress on ferroptosis as a potential therapeutic target. The mechanism of ferroptosis is related to intracellular iron metabolism level, lipid peroxide content, and glutathione peroxidase 4 activity. While ferroptosis holds promise as a therapeutic target for glioblastoma, its relation to other apoptosis methods is poorly understood and methods of applying ferroptosis to drug-resistant tumors are insufficiently explored.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Nikita Choudhary, Robert C. Osorio, Jun Y. Oh, Manish K. Aghi
Summary: Glioblastoma (GBM) is an aggressive brain tumor with limited prognosis despite multimodal treatment approaches. Various immunotherapies have been investigated to address the need for novel therapeutic options in GBM with limited success. Recently, alterations in the metabolism of cancer cells which allow for tumor proliferation, but simultaneously alter immune populations leading to an immunosuppressive tumor microenvironment, have been investigated as contributory to therapeutic resistance.
Review
Cell Biology
Xue-min Gao, Jian Li, Xin-xin Cao
Summary: This review summarizes the landscape of MAPK pathway mutations, their pathogenic roles, and potential treatment opportunities in Langerhans cell histiocytosis.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Oncology
Michala G. Rolver, Lya K. K. Holland, Muthulakshmi Ponniah, Nanditha S. Prasad, Jiayi Yao, Julie Schnipper, Signe Kramer, Line Elingaard-Larsen, Elena Pedraz-Cuesta, Bin Liu, Luis A. Pardo, Kenji Maeda, Albin Sandelin, Stine Falsig Pedersen
Summary: The mechanisms connecting acidic tumor microenvironments to disease progression are not yet fully understood. This study reveals that cancer cells adapted to an acidic pH environment exhibit increased capacity for acid extrusion and higher intracellular pH at physiological pH levels. This adaptation is associated with metabolic changes favoring oxidative metabolism, increased lipid content, peroxisome proliferation, and mitochondrial fusion. The upregulation of PPAR alpha, stimulated by increased fatty acid uptake, drives the metabolic changes by promoting mitochondrial and peroxisomal energy metabolism while limiting glycolysis. Inhibition of PPAR alpha results in increased sensitivity of acid-adapted cancer cells.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Cell Biology
Junfeng Bi, Atif Khan, Jun Tang, Aaron M. Armando, Sihan Wu, Wei Zhang, Ryan C. Gimple, Alex Reed, Hui Jing, Tomoyuki Koga, Ivy Tsz-Lo Wong, Yuchao Gu, Shunichiro Miki, Huijun Yang, Briana Prager, Ellis J. Curtis, Derek A. Wainwright, Frank B. Furnari, Jeremy N. Rich, Timothy F. Cloughesy, Harley I. Kornblum, Oswald Quehenberger, Andrey Rzhetsky, Benjamin F. Cravatt, Paul S. Mischel
Summary: The study identified SMPD1 as a drug target in GBM, and found that the antidepressant fluoxetine can inhibit SMPD1 activity, kill GBM cells, and enhance the effects of temozolomide treatment, leading to complete tumor regression. Real-world evidence also showed significantly increased survival in GBM patients treated with fluoxetine.
Article
Cell Biology
Xiao-Ning Zhang, Kai-Di Yang, Cong Chen, Zhi-Cheng He, Qiang-Hu Wang, Hua Feng, Sheng-Qing Lv, Yan Wang, Min Mao, Qing Liu, Yao-Yao Tan, Wen-Ying Wang, Tian-Ran Li, Lin-Rong Che, Zhong-Yi Qin, Ling-Xiang Wu, Min Luo, Chun-Hua Luo, Yu-Qi Liu, Wen Yin, Chao Wang, Hai-Tao Guo, Qing-Rui Li, Bin Wang, Wei Chen, Shuang Wang, Yu Shi, Xiu-Wu Bian, Yi-Fang Ping
Summary: The study reveals the role of pericytes in potentiating DDR signaling in GBM cells, and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.
Article
Cell Biology
Yubo Zhao, Jian Song, Weiwei Dong, Xiaobai Liu, Chunqing Yang, Di Wang, Yixue Xue, Xuelei Ruan, Libo Liu, Ping Wang, Mengyang Zhang, Yunhui Liu
Summary: The MBNL1/circNTRK2/PAX5 pathway plays a crucial role in regulating glycolysis in GBM and could provide potential targets and alternative strategies for the treatment of GBM.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Pedro Reimunde, Alba Pensado-Lopez, Martin Carreira Crende, Vanesa Lombao Iglesias, Laura Sanchez, Marta Torrecilla-Parra, Cristina M. Ramirez, Clement Anfray, Fernando Torres Andon
Summary: Glioblastoma (GBM) is a highly challenging brain tumor with poor prognosis and limited treatment options. Research on cellular heterogeneity and genetic alterations has led to the development of zebrafish models for studying GBM physiopathology and testing new drugs, offering hope for improved diagnosis and treatment outcomes.
Article
Oncology
Jeffrey A. Zuccato, Vikas Patil, Sheila Mansouri, Jeffrey C. Liu, Farshad Nassiri, Yasin Mamatjan, Ankur Chakravarthy, Shirin Karimi, Joao Paulo Almeida, Anne-Laure Bernat, Mohammed Hasen, Olivia Singh, Shahbaz Khan, Thomas Kislinger, Namita Sinha, Sebastien Froelich, Homa Adle-Biassette, Kenneth D. Aldape, Daniel D. De Carvalho, Gelareh Zadeh
Summary: This study identifies prognostic epigenetic chordoma subtypes using plasma methylomes and may transform patient management by balancing treatment aggressiveness with patient risk according to prognosis. Plasma methylomes can distinguish chordomas from other clinical diagnoses and accurately classify tumors based on plasma methylation data.
Article
Cell Biology
Deguan Lv, Ryan C. Gimple, Cuiqing Zhong, Qiulian Wu, Kailin Yang, Briana C. Prager, Bhaskar Godugu, Zhixin Qiu, Linjie Zhao, Guoxin Zhang, Deobrat Dixit, Derrick Lee, Jia Z. Shen, Xiqing Li, Qi Xie, Xiuxing Wang, Sameer Agnihotri, Jeremy N. Rich
Summary: Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. PDGF signaling induces m(6)A accumulation in GBM stem cells to regulate mitophagy. PDGF-METTL3-OPTN signaling is identified as a therapeutic target for GBM treatment.
DEVELOPMENTAL CELL
(2022)
Editorial Material
Oncology
James Felker, Sameer Agnihotri
Article
Oncology
Eshini Panditharatna, Joana G. Marques, Tingjian Wang, Maria C. Trissal, Ilon Liu, Li Jiang, Alexander Beck, Andrew Groves, Neekesh Dharia, Deyao Li, Samantha E. Hoffman, Guillaume Kugener, McKenzie L. Shaw, Hafsa M. Mire, Olivia A. Hack, Joshua M. Dempster, Caleb Lareau, Lingling Dai, Logan H. Sigua, Michael A. Quezada, Ann-Catherine J. Stanton, Meghan Wyatt, Zohra Kalani, Amy Goodale, Francisca Vazquez, Federica Piccioni, John G. Doench, David E. Root, Jamie N. Anastas, Kristen L. Jones, Amy Saur Conway, Sylwia Stopka, Michael S. Regan, Yu Liang, Hyuk-Soo Seo, Kijun Song, Puspalata Bashyal, William P. Jerome, Nathan D. Mathewson, Sirano Dhe-Paganon, Mario L. Suva, Angel M. Carcaboso, Cinzia Lavarino, Jaume Mora, Quang-De Nguyen, Keith L. Ligon, Yang Shi, Sameer Agnihotri, Nathalie Y. R. Agar, Kimberly Stegmaier, Charles D. Stiles, Michelle Monje, Todd R. Golub, Jun Qi, Mariella G. Filbin
Summary: This article introduces a new treatment strategy for H3K27M gliomas by inhibiting the BAF complex, which promotes differentiation and improves survival in patients.
Review
Clinical Neurology
Nishant Agrawal, Zachary C. Gersey, Hussam Abou-Al-Shaar, Paul A. Gardner, Megan Mantica, Sameer Agnihotri, Hussain Mahmud, Pouneh K. Fazeli, Georgios A. Zenonos
Summary: This article summarizes the genetic abnormalities and subcategories of pituitary adenomas (PAs). It provides comprehensive information on the genetic landscape of PAs, including genes, copy number variations, and microRNAs.
WORLD NEUROSURGERY
(2023)
Review
Oncology
Stephen C. C. Frederico, Corbin Darling, Xiaoran Zhang, Sakibul Huq, Sameer Agnihotri, Paul A. A. Gardner, Carl H. H. Snyderman, Eric W. W. Wang, Georgios A. A. Zenonos
Summary: Chordomas are locally invasive, low-grade CNS malignancies that are challenging to treat due to their invasiveness, resistance to treatment, and difficulty in achieving complete resection. Circulating-tumor DNA (ctDNA) monitoring has shown to be more sensitive in predicting residual tumor compared to imaging, allowing for earlier detection of incomplete resection or recurrence and potentially improving patient outcomes.
FRONTIERS IN ONCOLOGY
(2022)
Article
Genetics & Heredity
Ilon Liu, Li Jiang, Erik R. Samuelsson, Sergio Marco Salas, Alexander Beck, Olivia A. Hack, Daeun Jeong, McKenzie L. Shaw, Bernhard Englinger, Jenna LaBelle, Hafsa M. Mire, Sibylle Madlener, Lisa Mayr, Michael A. Quezada, Maria Trissal, Eshini Panditharatna, Kati J. Ernst, Jayne Vogelzang, Taylor A. Gatesman, Matthew E. Halbert, Hana Palova, Petra Pokorna, Jaroslav Sterba, Ondrej Slaby, Rene Geyeregger, Aaron Diaz, Izac J. Findlay, Matthew D. Dun, Adam Resnick, Mario L. Suva, David T. W. Jones, Sameer Agnihotri, Jessica Svedlund, Carl Koschmann, Christine Haberler, Thomas Czech, Irene Slavc, Jennifer A. Cotter, Keith L. Ligon, Sanda Alexandrescu, W. K. Alfred Yung, Isabel Arrillaga-Romany, Johannes Gojo, Michelle Monje, Mats Nilsson, Mariella G. Filbin
Summary: By analyzing the single-cell transcriptomics, epigenomics, and spatial architectures of a comprehensive cohort of H3-K27M DMGs, this study reveals the heterogeneity of these mutations at different ages and midline locations. The findings also provide insights into the cell-intrinsic and -extrinsic features of these tumors in relation to age and anatomical location, which can be used for rational modeling and therapeutic interventions.
Article
Oncology
Esther P. Jane, Matthew C. Reslink, Taylor A. Gatesman, Matthew E. Halbert, Tracy A. Miller, Brian J. Golbourn, Stephanie M. Casillo, Steven J. Mullett, Stacy G. Wendell, Udochukwu Obodo, Dinesh Mohanakrishnan, Riya Dange, Antony Michealraj, Charles Brenner, Sameer Agnihotri, Daniel R. Premkumar, Ian F. Pollack
Summary: In previous studies, the combination of panobinostat and bortezomib showed synergistic therapeutic activity against high-grade gliomas but resistance eventually emerged. In this study, the authors investigated the molecular mechanisms underlying the anticancer effects of panobinostat and marizomib, and identified glycolysis and the electron transport chain (ETC) as potential targets for overcoming resistance. In vivo experiments using a glycolysis and mitochondrial function inhibitor confirmed the efficacy of targeting these pathways. These findings provide new insights into treatment resistance in gliomas.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Danling Gu, Fengqi Zhou, Hao You, Jiancheng Gao, Tao Kang, Deobrat Dixit, Qiulian Wu, Kailin Yang, Shusheng Ci, Danyang Shan, Xiao Fan, Wei Yuan, Qian Zhang, Chenfei Lu, Daqi Li, Ningwei Zhao, Zhumei Shi, Wei Gao, Fan Lin, Jianghong Man, Qianghu Wang, Xu Qian, Stephen C. Mack, Weiwei Tao, Sameer Agnihotri, Nu Zhang, Yongping You, Jeremy N. Rich, Junxia Zhang, Xiuxing Wang
Summary: This study investigates the adaptive behavior of glioblastoma stem cells (GSCs) under different cholesterol supplies and finds that cholesterol biosynthetic enzymes are expressed at higher levels in the tumor core than in the invasive margins. The transcription factor SREBP2 promotes cholesterol biosynthesis, proliferation, self-renewal, and tumor growth in GSCs, and regulates the balance between cholesterol biosynthesis and uptake in different nutrient conditions. These findings provide important insights for a novel treatment strategy for glioblastoma.
Article
Medicine, Research & Experimental
Ryan C. Gimple, Guoxin Zhang, Shuai Wang, Tengfei Huang, Jina Lee, Suchet Taori, Deguan Lv, Deobrat Dixit, Matthew E. Halbert, Andrew R. Morton, Reilly L. Kidwell, Zhen Dong, Briana C. Prager, Leo J. Y. Kim, Zhixin Qiu, Linjie Zhao, Qi Xie, Qiulian Wu, Sameer Agnihotri, Jeremy N. Rich
Summary: In this study, the researchers found that SNX10 was selectively expressed in glioblastoma stem cells (GSCs) compared with non-neoplastic neural stem cells (NSCs). SNX10 was essential for GSC survival and promoted GSC proliferation and stem cell signaling pathways through posttranscriptional regulation of PDGFR tyrosine kinase. Targeting SNX10 expression decreased GSC viability and self-renewal capacity. High expression of SNX10 correlated with poor prognosis in glioblastoma patients.
Article
Oncology
Nicolina Jovanovich, Ahmed Habib, Jeffery Head, Farrukh Hameed, Sameer Agnihotri, Pascal O. Zinn
Summary: Diffuse midline glioma (DMG) is a pediatric cancer that has poor prognosis due to its infiltrative nature and protection from the blood-brain barrier. Epigenetic dysregulation, caused by a mutation in histone genes, leads to increased oncogenic potential in DMG cells. Standard treatments are not effective, and new therapeutics are needed. This review discusses the cell of origin, molecular mechanisms, standard care, and potential future therapeutics for DMG.
NEURO-ONCOLOGY ADVANCES
(2023)
Article
Oncology
Nicholas Mikolajewicz, Shahbaz Khan, Mara Trifoi, Anna Skakdoub, Vladmir Ignatchenko, Sheila Mansouri, Jeffrey Zuccatto, Brad E. Zacharia, Michael Glantz, Gelareh Zadeh, Jason Moffat, Thomas Kislinger, Alireza Mansouri
Summary: This study successfully identified diagnostic and prognostic biomarkers for glioblastoma, brain metastases, and primary central nervous system lymphoma through proteomic analysis of cerebrospinal fluid samples. Novel biomarkers were discovered, and the classification of tumors using low CSF volumes was found to be feasible for longitudinal tumor surveillance.
NEURO-ONCOLOGY ADVANCES
(2022)
Article
Oncology
Daniel F. Marker, Sameer Agnihotri, Nduka Amankulor, Geoffrey H. Murdoch, Thomas M. Pearce
Summary: Our study found that in IDH-mutant astrocytomas, the TP53 mutational spectrum is predominantly driven by a single hotspot mutation, which is not commonly found in IDH-wildtype astrocytomas. Tumors with TP53(R273C) mutation exhibit lower proliferation but tend to progress more quickly and have shorter survival, especially in male patients.
NEURO-ONCOLOGY ADVANCES
(2022)
Review
Oncology
Ryan C. Gimple, Kailin Yang, Matthew E. Halbert, Sameer Agnihotri, Jeremy N. Rich
Summary: This article reviews the molecular circuitry underlying adaptive plasticity in brain cancer stem cells. It discusses the transcriptional classification of the stem cell state, neoplastic evolution, development of therapeutic resilience, and the important role of the brain-specific microenvironment. The article emphasizes the dynamic nature of brain cancers and the ability of stem-like cells to respond and adapt to microenvironmental and therapeutic insults. Recent advancements in single-cell sequencing and a deeper understanding of the role of the immune system have provided new insights into potential therapeutic strategies.
NATURE REVIEWS CANCER
(2022)
Article
Oncology
Brian J. Golbourn, Matthew E. Halbert, Katharine Halligan, Srinidhi Varadharajan, Brian Krug, Nneka E. Mbah, Nisha Kabir, Ann-Catherine J. Stanton, Abigail L. Locke, Stephanie M. Casillo, Yanhua Zhao, Lauren M. Sanders, Allison Cheney, Steven J. Mullett, Apeng Chen, Michelle Wassell, Anthony Andren, Jennifer Perez, Esther P. Jane, Daniel R. David Premkumar, Robert F. Koncar, Shideh Mirhadi, Lauren H. McCarl, Yue-Fang Chang, Yijen L. Wu, Taylor A. Gatesman, Andrea F. Cruz, Michal Zapotocky, Baoli Hu, Gary Kohanbash, Xiuxing Wang, Alenoush Vartanian, Michael F. Moran, Frank Lieberman, Nduka M. Amankulor, Stacy G. Wendell, Olena M. Vaske, Ashok Panigrahy, James Felker, Kelsey C. Bertrand, Claudia L. Kleinman, Jeremy N. Rich, Robert M. Friedlander, Alberto Broniscer, Costas Lyssiotis, Nada Jabado, Ian F. Pollack, Stephen C. Mack, Sameer Agnihotri
Summary: Agnihotri and colleagues demonstrate that the loss of the MAT2A enzyme in the methionine cycle leads to a depletion of H3K36me3 and increases survival in glioma models. They identify MAT2A as a critical vulnerability in H3K27M gliomas through an RNA screen and show that the depletion of MAT2A reduces H3K36me3 levels, impacting oncogenic and developmental transcription programs. Methionine-restricted diets also extend survival in DMG models.