Article
Biochemistry & Molecular Biology
Qiong Wu, Anders E. Berglund, Robert J. Macaulay, Arnold B. Etame
Summary: This study provides evidence that the epigenetic reactivation of Tumor Suppressor Candidate 3 (TUSC3) can reprogram the sensitivity of glioblastoma stem cells (GSCs) to Temozolomide (TMZ), regardless of the promoter methylation status of the DNA repair gene O6-methylguanine DNA methyltransferase (MGMT). These findings offer a framework for further exploring TUSC3-mediated epigenetic reprogramming strategies to enhance TMZ sensitivity and outcomes in glioblastoma multiforme (GBM).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Neerada Meenakshi Warrier, Ramesh Kumar Krishnan, Vijendra Prabhu, Raghu Chandrashekhar Hariharapura, Prasoon Agarwal, Praveen Kumar
Summary: This study identifies survivin as a significant biomarker for glioblastoma multiforme cancer stem cells (GSCs) and demonstrates its importance in stemness, cancer progression, and therapy resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Cyntanna C. Hawkins, Amber B. Jones, Emily R. Gordon, Yuvika Harsh, Julia K. Ziebro, Christopher D. Willey, Corinne Griguer, David K. Crossman, Sara J. Cooper, Sasanka Ramanadham, Ninh Doan, Anita B. Hjelmeland
Summary: Sphingolipid metabolism is dysregulated in GBM, leading to cell evasion of apoptosis. This study found that the mRNA levels of acid ceramidase, a key enzyme in S1P production, were elevated in recurrent GBM. Inhibiting acid ceramidase decreased cell growth and increased apoptosis in TMZ-resistant GBM cells, suggesting the potential utility of targeting sphingolipid metabolism in recurrent GBM.
CELL DEATH DISCOVERY
(2023)
Article
Oncology
Beiwu Lan, Hongyang Zhao, Yichun He, Zenghui Zhao, Nang Wang, Yufei Gao
Summary: This study found that inhibition of HsPDF can suppress the expression of mtDNA-encoded proteins in GBM cells, and promote mitochondrial apoptosis by decreasing OXPHOS level, disrupting mitochondrial protein homeostasis, increasing mitochondrial fission and activating the integrated stress response.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Nan Wang, Peining Zhu, Renxuan Huang, Liankun Sun, Delu Dong, Yufei Gao
Summary: This study investigated the effects of combined treatment with G-TPP and TMZ on GBM cells by suppressing the function of TRAP1. The results showed that suppressing TRAP1 induced mtUPR, leading to a burst of ROS and sensitizing GBM cells to TMZ treatment.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Plant Sciences
Qingfa Tang, Haihong Cao, Ni Tong, Yuanliang Liu, Wanyu Wang, Yuheng Zou, Lanyang Xu, Zhiyun Zeng, Wei Xu, Zhixin Yin, Wenjuan Ma, Qirui Wang
Summary: This study demonstrates that traditional Chinese medicine tubeimoside-I (TBMS1) has a synergistic therapeutic effect against TMZ-resistant glioblastoma multiforme by promoting apoptosis and inhibiting cell proliferation.
Article
Biochemistry & Molecular Biology
Mengdong Ni, Jiajia Li, Haiyun Zhao, Fei Xu, Jingyi Cheng, Min Yu, Guihao Ke, Xiaohua Wu
Summary: Cisplatin-based chemoradiotherapy is recommended for treating local advanced cervical cancer, but radioresistance remains a clinical challenge. Aberrant epigenetic modifications have been identified as a key factor in the development of radioresistance. In this study, JQ1, a BRD4 inhibitor, was identified as a potent radiosensitizer for cervical cancer, with BRD4 inhibition sensitizing cancer cells to radiotherapy by inhibiting RAD51AP1 transcription. High BRD4 expression is associated with poor prognosis and radiation resistance.
Article
Biotechnology & Applied Microbiology
Jingru Che, Thomas J. DePalma, Hemamylammal Sivakumar, Louisa S. Mezache, Miranda M. Tallman, Monica Venere, Katelyn Swindle-Reilly, Rengasayee Veeraraghavan, Aleksander Skardal
Summary: Glioblastoma (GBM) is a common and aggressive form of brain cancer with poor prognosis due to resistance to the most commonly used chemotherapy. Recent studies have shown that high expression of connexin 43 (Cx43) in GBM is associated with worse patient outcomes. In this study, researchers used a three-dimensional organoid model to demonstrate that combined treatment with a Cx43 mimetic peptide, alpha CT1, and TMZ significantly improved treatment efficacy for certain populations of GBM. These findings suggest that inhibiting Cx43 could be a promising approach for improving GBM treatment.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Katharina Otte, Kai Zhao, Madita Braun, Andreas Neubauer, Hartmann Raifer, Frederik Helmprobst, Felipe Ovalle Barrera, Christopher Nimsky, Joerg W. Bartsch, Tillmann Rusch
Summary: This study found that Eltanexor, a second-generation XPO1 inhibitor, has effective monotherapy effects on GBM cells and can be combined with current adjuvant therapies to provide a more effective treatment for GBM. The mechanism of Eltanexor-induced apoptosis in GBM cells may be related to increased expression of TP53-dependent genes.
Article
Biochemistry & Molecular Biology
Jonas Feldheim, Almuth F. Kessler, Julia J. Feldheim, Ellina Schulz, David Wend, Lazaros Lazaridis, Christoph Kleinschnitz, Martin Glas, Ralf-Ingo Ernestus, Sebastian Brandner, Camelia M. Monoranu, Mario Loehr, Carsten Hagemann
Summary: Glioblastoma is a fatal tumor and chemotherapy with temozolomide (TMZ) is a crucial treatment. However, TMZ treatment may lead to changes in MGMT promoter methylation and affect the migration and proliferation behavior of tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Alexandra M. Amen, Christof Fellmann, Katarzyna M. Soczek, Shawn M. Ren, Rachel J. Lew, Gavin J. Knott, Jesslyn E. Park, Andrew M. McKinney, Andrew Mancini, Jennifer A. Doudna, Joseph F. Costello
Summary: Mutations in the TERT promoter of glioblastomas create binding sites for GABP transcription factor complexes, leading to reactivation of TERT and maintenance of telomeres. GBM cells with TERT promoter mutations display a dependence on GABPB1L for proliferation, which can be rescued by upregulation of the protein paralogue GABPB2. Inhibition of GABPB1L in combination with chemotherapy results in reduced growth of intracranial GBM tumors by impairing DNA damage response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Konstantin R. Brawanski, Susanne Sprung, Christian F. Freyschlag, Romana Hoeftberger, Thomas Stroebel, Johannes Haybaeck, Claudius Thome, Claudia Manzl, Anna M. Birkl-Toeglhofer
Summary: This study investigated the associations between MGMT promoter methylation, MGMT and MMR protein expression, and their effect on overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma. The results showed that MGMT promoter methylation is associated with improved OS in glioblastoma patients younger than 70 years old, while the extent of surgery has a larger impact on overall survival in elderly patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Moli Wu, Danyang Song, Hui Li, Nisar Ahmad, Hong Xu, Xiaobo Yang, Qian Wang, Xiaoxin Cheng, Sa Deng, Xiaohong Shu
Summary: Chemoresistance is a challenge in the treatment of glioblastoma (GBM), and the activity of O6-methylguanine-DNA methyltransferase (MGMT) and signal transducer and of transcription 3 (STAT3) have been linked to GBM resistance. Resveratrol (Res) inhibits tumor growth and improves chemosensitivity by targeting STAT3 signaling. This study found that Res effectively improved chemosensitivity of GBM cells to temozolomide (TMZ) and downregulated STAT3 activity, leading to inhibition of cell proliferation, migration, and induction of apoptosis. The combination therapy of Res and TMZ also reversed TMZ resistance and decreased MGMT and STAT3 levels. Therefore, Res may be an ideal candidate for combined chemotherapy with TMZ in GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Maria Joao Ramalho, Ines David Torres, Joana Angelica Loureiro, Jorge Lima, Maria Carmo Pereira
Summary: This study proposes a method of co-delivering temozolomide and bortezomib to glioblastoma cells through nanoparticles, which overcomes the limitations of current therapeutic strategies. The results show that this method significantly inhibits tumor cell survival and proliferation with low toxicity.
ACS APPLIED NANO MATERIALS
(2023)
Article
Oncology
Martin Glas, Matthew T. Ballo, Ze'ev Bomzon, Noa Urman, Shay Levi, Gitit Lavy-Shahaf, Suriya Jeyapalan, Terence T. Sio, Paul M. DeRose, Martin Misch, Sophie Taillibert, Zvi Ram, Andreas F. Hottinger, Jacob Easaw, Chae-Yong Kim, Suyash Mohan, Roger Stupp
Summary: TTFields treatment affects the rate of distant progression in newly diagnosed GBM patients, with distant lesions appearing further from the primary lesion in the TTFields treatment arm. Distant progression correlates with improved clinical outcomes in TTFields patients.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Correction
Oncology
Michael Weller, Martin van den Bent, Matthias Preusser, Emilie Le Rhun, Jorg C. Tonn, Giuseppe Minniti, Martin Bendszus, Carmen Balana, Olivier Chinot, Linda Dirven, Pim French, Monika E. Hegi, Asgeir S. Jakola, Michael Platten, Patrick Roth, Roberta Ruda, Susan Short, Marion Smits, Martin J. B. Taphoorn, Andreas von Deimling, Manfred Westphal, Riccardo Soffietti, Guido Reifenberger, Wolfgang Wick
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Article
Neurosciences
Pierre Bady, Christine Marosi, Michael Weller, Bjorn H. Gronberg, Henrik Schultz, Martin J. B. Taphoorn, Johanna M. M. Gijtenbeek, Martin J. van den Bent, Andreas von Deimling, Roger Stupp, Annika Malmstroem, Monika E. Hegi
Summary: This study aimed to identify age-related molecular differences in elderly glioblastoma patients and guide treatment decisions. The researchers found that DNA methylation features were associated with tumor classification, but not age. Furthermore, there was no molecular evidence to support different treatments for elderly patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Oncology
Lea Beltzig, Christian Schwarzenbach, Petra Leukel, Katrin B. M. Frauenknecht, Clemens Sommer, Alessandro Tancredi, Monika E. Hegi, Markus Christmann, Bernd Kaina
Summary: In the treatment of glioblastoma, cellular senescence induced by DNA damage is found to be more important than apoptosis. The primary trigger of cellular senescence is DNA damage, rather than apoptosis. Cells that acquire resistance to treatment also become resistant to the induction of senescence. Induction of cellular senescence during treatment may play a significant role in therapy resistance.
Article
Cell Biology
Girieca Lorusso, Christof B. Wyss, Francois Kuonen, Nicola Vannini, Clotilde Billottet, Nathalie Duffey, Raphael Pineau, Qiang Lan, Pratyaksha Wirapati, David Barras, Alessandro Tancredi, Ruth Lyck, Hans-Anton Lehr, Britta Engelhardt, Mauro Delorenzi, Andreas Bikfalvi, Curzio Ruegg
Summary: This study reports a spontaneous model of breast cancer metastasis to the brain and identifies Cx-mediated FAK-NF-κB signaling as a mechanism promoting cell-autonomous and microenvironmentally controlled cell survival for brain colonization.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
David Capper, Guido Reifenberger, Pim J. French, Leonille Schweizer, Michael Weller, Mehdi Touat, Simone P. Niclou, Philipp Euskirchen, Christine Haberler, Monika E. Hegi, Sebastian Brandner, Emilie Le Rhun, Roberta Ruda, Marc Sanson, Ghazaleh Tabatabai, Felix Sahm, Patrick Y. Wen, Pieter Wesseling, Matthias Preusser, Martin J. van den Bent
Summary: The mainstay of treatment for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a part of the standard of care, however, the predictive significance of most of these targets in central nervous system (CNS) tumors remains less well-studied.
Article
Cell Biology
Angel F. Alvarez-Prado, Roeltje R. Maas, Klara Soukup, Florian Klemm, Mara Kornete, Fanny S. Krebs, Vincent Zoete, Sabina Berezowska, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce
Summary: Brain metastases (BrMs) are a common type of brain tumor in adults, usually originating from lung and breast primary cancers. Effective therapies are needed due to the high mortality rate associated with BrMs. Genetic profiling of primary tumors is used to guide targeted therapies against BrMs, and immune-based strategies for metastatic cancer treatment are gaining momentum. However, the tumor immune microenvironment (TIME) of BrMs is heterogeneous and it is unknown whether specific genetic profiles are associated with distinct immune states. In this study, the immunogenomic landscape of human BrMs was extensively characterized, revealing unique TIME phenotypes in genetically distinct lung- and breast-BrMs, which allows for the development of personalized immunotherapies based on the genetic makeup of the tumors.
CELL REPORTS MEDICINE
(2023)
Review
Oncology
Felix Sahm, Sebastian Brandner, Luca Bertero, David Capper, Pim J. French, Dominique Figarella-Branger, Felice Giangaspero, Christine Haberler, Monika E. Hegi, Bjarne W. Kristensen, Kathreena M. Kurian, Matthias Preusser, Bastiaan B. J. Tops, Martin van den Bent, Wolfgang Wick, Guido Reifenberger, Pieter Wesseling
Summary: In the 5th edition of the WHO CNS tumor classification, molecular characteristics have become important diagnostic criteria for many CNS tumor types. This guideline focuses on the methods used for diagnosing gliomas, glioneuronal, and neuronal tumors using informative molecular markers. Various molecular methods are discussed, including next-generation sequencing, methylation profiling, and immunohistochemistry. The guideline also covers the analysis of MGMT promoter methylation status, and provides an overview of the advantages, limitations, and requirements of different assays. The importance of molecular diagnostic testing in neuro-oncology is emphasized, along with discussions on clinical relevance, accessibility, cost, and ethical aspects.
Article
Oncology
Vladimir Wischnewski, Roeltje R. Maas, Paola Guerrero Aruffo, Klara Soukup, Giovanni Galletti, Mara Kornete, Sabine Galland, Nadine Fournier, Johanna Lilja, Pratyaksha Wirapati, Joao Lourenco, Alice Scarpa, Roy T. Daniel, Andreas F. Hottinger, Jean-Philippe Brouland, Agnese Losurdo, Emanuele Voulaz, Marco Alloisio, Monika E. Hegi, Enrico Lugli, Johanna A. Joyce
Summary: The authors used T cell profiling in brain tumor samples to understand the biology and therapeutic relevance of the brain tumor microenvironment. They found a tissue-specific conflict between immune suppression and immune activation in brain tumors, which can inform stratification for immunotherapy. Their analysis revealed differences in T cell biology between individuals, with a subgroup of brain metastases showing accumulation of potentially tumor-reactive T cells.
Article
Oncology
Thi Tham Nguyen, Premnath Rajakannu, Minh Dieu Thanh Pham, Leo Weman, Alexander Jucht, Michelle C. Buri, Kristof Van Dommelen, Monika E. Hegi
Summary: Glioblastoma, a highly malignant brain tumor, exhibits characteristic epigenetic alterations, including the recurrent silencing of the HTATIP2 gene, which affects the nuclear localization of the DNA repair enzyme MPG. The reduced nuclear localization of MPG leads to decreased repair of treatment-induced DNA lesions, contributing to treatment resistance in glioblastoma.
MOLECULAR ONCOLOGY
(2023)
Letter
Oncology
Sylvia C. Kurz, Anja Stammberger, Steffen K. Rosahl, Lauren E. Abrey, Nathalie L. Albert, Louisa von Baumgarten, Jens Gempt, Anca-L Grosu, Verena Leidgens, Anna McLean, Mirjam Renovanz, Julia Schwarzenberger, Lisa Sevenich, Tadeja Urbanic Purkart, Stephanie E. Combs, Ghazaleh Tabatabai, Monika Hegi, Martha Nowosielski
Meeting Abstract
Oncology
Alessandro Tancredi, Olga Gusyatiner, Pierre Bady, Michelle Buri, Remy Lomazzi, Davide Chiesi, Monika Hegi