Review
Biochemistry & Molecular Biology
Safwan Alomari, Irma Zhang, Adrian Hernandez, Caitlin Y. Kraft, Divyaansh Raj, Jayanidhi Kedda, Betty Tyler
Summary: Glioblastoma is a common malignant brain tumor with poor prognosis, and there is a need for effective therapeutics. Drug repurposing is a potential strategy, with some drugs showing efficacy against GBM cell lines. However, the blood-brain barrier may limit their effectiveness.
Article
Chemistry, Multidisciplinary
Jiantang Liang, Lei Li, Hailong Tian, Zhihan Wang, Guowen Liu, Xirui Duan, Meiwen Guo, Jiaqi Liu, Wei Zhang, Edouard C. Nice, Canhua Huang, Weifeng He, Haiyuan Zhang, Qifu Li
Summary: Developing therapies that can effectively target glioblastoma by crossing the blood-brain barrier (BBB) and induce ferroptosis is crucial for improving treatment outcomes. In this study, a versatile biomimetic nanoplatform, L-D-I/NPs, was designed for selective targeting of glioblastoma by binding to low-density lipoprotein receptor-related protein-1 (LRP1) and crossing the BBB, thus inducing ferroptosis in glioblastoma cells. L-D-I/NPs have demonstrated the ability to effectively suppress tumor progression and prolong survival in a mouse glioblastoma model, offering a promising approach for ferroptosis-based therapies.
Review
Pharmacology & Pharmacy
Vigneshwaran Namasivayam, Senthikumar Palaniappan, Murugesan Vanangamudi
Summary: Researchers face challenges in developing treatments for emerging and re-emerging epidemic infections. Drug repurposing is a reliable strategy for discovering new antiviral agents quickly and reducing the need for clinical trials.
DRUG DISCOVERY TODAY
(2022)
Article
Oncology
Xu Yang, Yan Zhang, Zhiwei Xue, Yaotian Hu, Wenjing Zhou, Zhiyi Xue, Xuemeng Liu, Guowei Liu, Wenjie Li, Xiaofei Liu, Xingang Li, Mingzhi Han, Jian Wang
Summary: This study found an increased expression of TRIM56 in glioblastoma, which promoted glioma progression by stabilizing cIAP1 through deubiquitination. The interaction between TRIM56 and cIAP1 may play a key role in glioma development. Additionally, TRIM56 could serve as a potential therapeutic molecular target and prognostic indicator for glioblastoma patients.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, Research & Experimental
Wei-Zhi Lin, Yen-Chun Liu, Meng-Chang Lee, Chi-Tun Tang, Gwo-Jang Wu, Yu-Tien Chang, Chi-Ming Chu, Chia-Yang Shiau
Summary: This study identified 12 candidate drugs for the potential treatment of glioblastoma based on genome-wide association studies. The results showed that these candidate drugs were more effective in inhibiting glioma cell lines compared to the standard treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Lisa Zirjacks, Nicolai Stransky, Lukas Klumpp, Lukas Prause, Franziska Eckert, Daniel Zips, Sabine Schleicher, Rupert Handgretinger, Stephan M. Huber, Katrin Ganser
Summary: The study demonstrated that disulfiram (DSF) has tumoricidal and therapy-sensitizing effects on glioblastoma stem cells (GSCs) independent of ALDH1A3 expression, but its effects are dampened when used in combination with temozolomide.
Review
Chemistry, Multidisciplinary
Qiujun Qiu, Xinyi Ding, Jixiang Chen, Sunhui Chen, Jianxin Wang
Summary: Gliomas are aggressive and lethal tumors for which there are few treatment options. Nanobiotechnology offers promising strategies for early diagnosis, postoperative regrowth suppression, and microenvironment remodeling. It has the potential to address the challenges of managing recurrent glioma and accelerating drug development.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Oncology
Monserrat Llaguno-Munive, Maria Ines Vazquez-Lopez, Rafael Jurado, Patricia Garcia-Lopez
Summary: Glioma is the most common and aggressive primary tumor of the central nervous system, with standard treatment often failing to achieve desired results. Researchers are exploring the potential of using anti-hormonal agents like mifepristone as a new approach to glioma treatment.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
U. Jisha Pillai, Anindita Ray, Meenu Maan, Mainak Dutta
Summary: The identification of new drugs for cancer treatment faces hurdles, leading to an increasing interest in drug repurposing, which involves using old drugs for new therapeutic purposes. This approach is cost-effective and enables fast clinical translation. As cancer is also considered a metabolic disease, drugs approved for metabolic disorders, such as diabetes and cardiovascular disease (CVD), are being actively repurposed for anticancer treatment. This review discusses the repurposing of these drugs and highlights their targeting of cancer signaling pathways.
DRUG DISCOVERY TODAY
(2023)
Article
Multidisciplinary Sciences
Ken Miyaguchi, Hongqiang Wang, Keith L. Black, Stephen L. Shiao, Rongfu Wang, John S. Yu
Summary: Efficient activation of T cells with tumor-associated antigens (TAAs) to glioblastoma (GBM) stem cells was achieved through the use of three different antigen sources loaded onto dendritic cells (DCs). An activated T cell (ATC) protocol was developed and optimized for a phase I clinical trial to target GSCs. The synthetic peptide pool loading method showed significantly increased cytotoxicity towards target cells.
SCIENTIFIC REPORTS
(2023)
Review
Medicine, Research & Experimental
Jason Miska, Navdeep S. Chandel
Summary: Glioblastoma (GBM) is a highly lethal brain tumor that is resistant to conventional therapies. Recent research has focused on understanding the metabolic processes involved in GBM, particularly fatty acid (FA) metabolism. These processes can be classified into four broad fates: synthesis, degradation, regulation of ferroptosis, and generation of signaling molecules. This Review provides insights into each of these fates and highlights the need for further understanding and untangling of the complex FA metabolism in GBM.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Xiaoping Hu, Jingdun Xie, Yilin Yang, Ziyi Qiu, Weicheng Lu, Xudong Lin, Bingzhe Xu
Summary: Researchers established a Multi-Target Neural Differentiation (MTND) therapeutic cocktail to effectively and safely treat brain malignancies by targeting poor cell differentiation and compromised cell cycle in brain cancers. In-vitro and in-vivo experiments demonstrated the significant therapeutic effect of MTND therapy, with improved outcomes compared to current chemo-drugs. MTND induced neural conversion of glioma cells, controlled the cell cycle, and reduced tumor growth, offering new avenues for brain malignancy treatments beyond cytotoxic agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Hongtao Zhu, Xingjiang Yu, Suojun Zhang, Kai Shu
Summary: The complement system plays a significant role in the development of malignant glioma and may serve as potential therapeutic targets and prognostic factors. Specifically targeting the complement system could be of great significance in future treatments for various types of tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Anjali Yadav, Ali Alnakhli, Hari Priya Vemana, Shraddha Bhutkar, Aaron Muth, Vikas V. Dukhande
Summary: This study discovered that stiripentol (STP) is an effective therapeutic for glioblastoma multiforme (GBM). STP decreased GBM cell viability, proliferation, clonogenic ability, and migration. It also showed effectiveness in 3D spheroid models and TMZ-resistant cells. Furthermore, STP had additive or synergistic effects with TMZ and was less toxic to normal cells.
PHARMACEUTICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Tianduanyi Wang, Otto I. Pulkkinen, Tero Aittokallio
Summary: Most drug molecules have the ability to modulate multiple target proteins, which can lead to both therapeutic effects and unwanted side effects. Evaluating the selectivity of a compound is an important factor in drug development and repurposing efforts. Traditional methods for characterizing selectivity fall short in quantifying how selective a compound is against a particular target protein. In this study, we propose an optimization-based selectivity scoring method that allows for the identification of potent and selective compounds against given kinase targets. We demonstrate the effectiveness of this method in finding highly selective compounds in computational experiments using a large-scale kinase inhibitor dataset.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Article
Cell Biology
Trang T. T. Nguyen, Yiru Zhang, Enyuan Shang, Chang Shu, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Editorial Material
Biochemistry & Molecular Biology
Mike-Andrew Westhoff, Tim Baisch, Verena J. Herbener, Georg Karpel-Massler, Klaus-Michael Debatin, Hannah Strobel
Review
Biochemistry & Molecular Biology
Verena J. Herbener, Timo Burster, Alicia Goreth, Maximilian Pruss, Helene von Bandemer, Tim Baisch, Rahel Fitzel, Markus D. Siegelin, Georg Karpel-Massler, Klaus-Michael Debatin, Mike-Andrew Westhoff, Hannah Strobel
Article
Chemistry, Medicinal
Matthias Schneider, Anna-Laura Potthoff, Bernd O. Evert, Marius Dicks, Denise Ehrentraut, Andreas Dolf, Elena N. C. Schmidt, Niklas Schaefer, Valeri Borger, Torsten Pietsch, Mike-Andrew Westhoff, Erdem Guresir, Andreas Waha, Hartmut Vatter, Dieter H. Heiland, Patrick Schuss, Ulrich Herrlinger
Summary: Inhibition of intercellular cytosolic traffic via gap junctions enhances the antitumoral effects of lomustine, regardless of MGMT promoter methylation status, providing a clinically-feasible way to profoundly augment chemotherapeutic effects for all glioblastoma patients, with growing interest in lomustine as a first and second line therapy for glioblastoma.
Article
Multidisciplinary Sciences
Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin
Summary: The inhibition of AURKA can lead to metabolic reprogramming in glioblastoma cells, enhancing mitochondrial activity, and inhibiting oxidative metabolism can sensitize the cells. Combining AURKA inhibitors with FAO inhibitors extends overall survival in GBM models.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Carolin Golla, Mayas Bilal, Annika Dwucet, Nicolas Bader, Jenson Anthonymuthu, Tim Heiland, Maximilian Pruss, Mike-Andrew Westhoff, Markus David Siegelin, Felix Capanni, Christian Rainer Wirtz, Richard Eric Kast, Marc-Eric Halatsch, Georg Karpel-Massler
Summary: The combination of photodynamic therapy and ABT-263 exhibited synergistic antineoplastic effects on glioblastoma cells, suggesting a potential benefit for treating this disease. The study aimed to enhance the biological effects of 5-aminolevulinic acid-based photodynamic therapy by inhibiting Bcl-2/Bcl-xL proteins in different glioblastoma models. Further investigation is warranted based on the promising results.
Review
Cell Biology
Timo Burster, Rebecca Traut, Zhanerke Yermekkyzy, Katja Mayer, Mike-Andrew Westhoff, Joachim Bischof, Uwe Knippschild
Summary: The invasive nature of glioblastoma poses challenges to standard care, as conventional therapies have failed to completely eradicate glioblastoma cells. New approaches including small molecule inhibitors, immunotherapy, and virotherapy, focus on boosting the host immune system to interfere with immune evasion of glioblastoma cells, showing promise for therapeutic applications.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Mike-Andrew Westhoff, Marie Schuler-Ortoli, Daniela Zerrinius, Amina Hadzalic, Andrea Schuster, Hannah Strobel, Angelika Scheuerle, Tiana Wong, Christian Rainer Wirtz, Klaus-Michael Debatin, Aurelia Peraud
Summary: Medulloblastoma is a common solid tumor in children, and current treatments are not highly effective. Modulating the Bcl-2 family members could potentially improve the treatment outcomes by inhibiting tumor cells' resistance to apoptosis.
Article
Oncology
Trang T. T. Nguyen, Enyuan Shang, Salveena Schiffgens, Consuelo Torrini, Chang Shu, Hasan Orhan Akman, Varun V. Prabhu, Joshua E. Allen, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Summary: A novel synthetic lethal interaction between ClpP activation and HDAC1/2 inhibition has been identified to impact the energy metabolism of glioblastoma (GBM). The combined treatment of ClpP activators and HDAC inhibitors shows promise in significantly reducing GBM cell viability and prolonging host survival.
CLINICAL CANCER RESEARCH
(2022)
Review
Cell Biology
Trang T. T. Nguyen, Enyuan Shang, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Summary: Glioblastoma, the most common primary brain tumor in adults, displays reprogrammed metabolism and utilizes various fuel sources. Blocking glycolysis may lead to the reactivation of beta-oxidation of fatty acids.
Article
Health Care Sciences & Services
Mike-Andrew Westhoff, Carsten Posovszky, Klaus-Michael Debatin
Summary: Vaccines are highly effective in saving lives, but unfortunately they are often met with more controversy than their safety profile justifies. The anti-vaccine movement has evolved through three generations, with the current generation being closely associated with the broader anti-COVID movement and promoting individualism over community health. It is crucial to provide better science education to the young and the general public to improve overall science literacy, and strategies to achieve this are suggested.
INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING
(2023)
Review
Medicine, Research & Experimental
Patricia Kattner, Katharina Zeiler, Verena J. Herbener, Katia La Ferla-Bruhl, Rebecca Kassubek, Michael Grunert, Timo Burster, Oliver Bruhl, Anna Sarah Weber, Hannah Strobel, Georg Karpel-Massler, Sibylle Ott, Alexa Hagedorn, Daniel Tews, Ansgar Schulz, Vikas Prasad, Markus D. Siegelin, Lisa Nonnenmacher, Pamela Fischer-Posovszky, Marc-Eric Halatsch, Klaus-Michael Debatin, Mike-Andrew Westhoff
Summary: Animal cancers offer a valuable reservoir of biomedical information with implications for human oncology. By studying tumor biology in non-human hosts, insights can be gained to improve cancer treatment strategies and potentially address Peto's Paradox.
Meeting Abstract
Oncology
Trang Nguyen, Enyuan Shang, Chang Shu, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Catarina Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey Bruce, Peter Canoll, Markus Siegelin