Review
Biochemistry & Molecular Biology
Manali Tilak, Jennifer Holborn, Laura A. New, Jasmin Lalonde, Nina Jones
Summary: Glioblastoma multiforme (GBM) is a deadly cancer with limited response to existing therapies. Subtypes of GBM with distinct genetic signatures show aberrant activation of signal transduction pathways. Current research focuses on understanding these molecular alterations to develop more efficient targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yung-Lung Chang, Yao-Feng Li, Chung-Hsing Chou, Li-Chun Huang, Yi-Ping Wu, Ying Kao, Chia-Kuang Tsai
Summary: Diosmin, a natural flavone glycoside, demonstrated inhibitory effects on GBM cell growth, migration, and invasion, as well as modulation of autophagy and cell cycle progression. It showed limited cytotoxicity towards astrocytes and holds potential for new GBM treatment therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Harpinder K. Brar, Jiney Jose, Zimei Wu, Manisha Sharma
Summary: This review explores the potential of targeted therapies, such as tyrosine kinase inhibitors (TKIs), in treating glioblastoma multiforme (GBM). It also analyzes the reasons why TKIs have been unsuccessful in clinical trials for GBM despite their success in treating other cancer types. The main focus is on promising drug delivery strategies, particularly the use of nanocarriers, to enhance the efficacy of TKIs in GBM by overcoming the limitations imposed by the blood-brain barrier.
Article
Biochemistry & Molecular Biology
Thushara W. Madanayake, Eric A. Welsh, Lancia N. F. Darville, John M. Koomen, Charles E. Chalfant, Eric B. Haura, Timothy J. Robinson
Summary: We have developed a novel method to inhibit EGFR signaling using custom ASOs to induce exon skipping and drive the expression of dominant negative mRNA isoforms of EGFR. Our in vivo experiments showed that ASOs were highly effective in inhibiting colony formation, cell viability, and migration in EGFR mutant NSCLC. Importantly, ASOs maintained their efficacy in erlotinib-resistant subclones and wild-type EGFR overexpressing models, where erlotinib had no significant effect. By directly targeting the EGFR kinase domain, ASOs resulted in maximal inhibition of EGFR phosphorylation and downstream signaling in both EGFR mutant and erlotinib-resistant cells. Furthermore, our study confirmed the EGFR-specific therapeutic mechanism of ASOs in EGFR-independent NSCLC models. Further investigation of the synergy between ASOs and existing tyrosine kinase inhibitors could provide new clinical models to improve EGFR-targeted therapies for NSCLC patients, both mutant and wild-type.
NUCLEIC ACID THERAPEUTICS
(2022)
Review
Oncology
Paula Aldaz, Imanol Arozarena
Summary: Glioblastoma (GBM) is the most common and lethal form of malignant brain tumor, and patients typically undergo surgery followed by radiotherapy and chemotherapy. Despite promising preclinical evidence, clinical trials testing the therapeutic potential of tyrosine kinase inhibitors (TKIs) targeting EGFR, PDGF receptors, and other tyrosine kinases have not led to significant breakthroughs in treating GBM over the past two decades. This article critically analyzes the reasons for the failure of TKIs in GBM treatment and proposes alternative approaches for the evaluation of TKIs in GBM patients.
Article
Biochemistry & Molecular Biology
Kostas A. Papavassiliou, Athanasios G. Papavassiliou
Summary: GBM, a deadly brain tumor, has limited treatment options and mTOR pathway plays a crucial role in its pathogenesis. Initial attempts with first-generation mTOR inhibitors lacked significant success in clinical trials, but the development of next-generation inhibitors offers new hope for the potential of mTOR inhibitors in GBM.
Article
Oncology
Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun
Summary: The study revealed that m6A controlled the interference of EMT features, the miR-146a/Notch signaling pathway was highly activated in an m6A-dependent manner, and TUSC7 regulation of miR-146a affected Notch signaling functions, influencing lung cancer progression and stem cell renewal.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biology
Sofija Jovanovic Stojanov, Ana Kostic, Mila Ljujic, Ema Lupsic, Silvia Schenone, Milica Pesic, Jelena Dinic
Summary: Drug resistance is a major challenge in treating glioblastoma. Autophagy plays a crucial role in drug resistance, and the use of autophagy inhibitors can enhance the effectiveness of targeted therapy. This study shows that two Src tyrosine kinase inhibitors can induce autophagy in glioblastoma cells, and inhibiting autophagy can increase the anticancer effects of these inhibitors.
Article
Biochemistry & Molecular Biology
Lea Scherschinski, Markus Prem, Irina Kremenetskaia, Ingeborg Tinhofer, Peter Vajkoczy, Anna-Gila Karbe, Julia Sophie Onken
Summary: The receptor tyrosine kinase AXL (RTK-AXL) plays a crucial role in therapy resistance in glioblastoma multiforme (GBM). The shedding product of RTK-AXL, CT-AXL, acts as a surrogate marker for radio-resistance. Overexpression of endogenous RTX-AXL leads to therapy resistance, but combination therapy of AXL TKI with standard treatments can increase therapeutic effects significantly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Barbara Brandt, Marica Nemeth, Gergely Berta, Mate Szunstein, Marija Heffer, Tibor A. Rauch, Marianna Pap
Summary: There is currently no effective therapy for the increasing incidence of GBM, and TMZ resistance is a major problem. However, combination treatment of MLN4924 and TMZ can decrease cell viability and sensitize TMZ-resistant cells, providing a new treatment strategy for GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Xu Zhang, Jie Wang, Yifeng Wang, Guanzheng Liu, Huan Li, Jiefeng Yu, Runqiu Wu, Jun Liang, Rutong Yu, Xuejiao Liu
Summary: MELK inhibitor OTSSP167 effectively inhibits proliferation of GBM cells, prolongs survival in mouse models, and suppresses growth and stemness properties of GSCs. Targeted inhibition of MELK shows potential as a novel treatment for GBM.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
Article
Pharmacology & Pharmacy
Xudong Zhang, Shengnan Jin, Xin Shi, Shengyu Liu, Kunhang Li, Guojun Liu, Shiyu Zhong, Tao Liu, Lishuai Li, Shanwei Tao, Qingqing Zhai, Nan Bao, Lijie Ren, Ying Wu, Yijun Bao
Summary: This study identified ten key genes associated with IDH1 status in GBM, established a ferroptosis-related prognostic model, and revealed the strong association of these genes with immune-related factors and key signaling pathways. The findings provide new insights into the prognosis and treatment of GBM patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Carolin Seifert, Ellen Balz, Susann Herzog, Anna Korolev, Sebastian Gassmann, Heiko Paland, Matthias A. Fink, Markus Grube, Sascha Marx, Gabriele Jedlitschky, Mladen Tzvetkov, Bernhard H. Rauch, Henry W. S. Schroeder, Sandra Bien-Moeller
Summary: Research has shown that PIM1 kinase plays a significant role in the behavior of glioblastoma stem cells, and its inhibition can lead to the death of these stem-like cells, suggesting a potential approach for glioblastoma therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Bobbie J. Rimel, Erin K. Crane, June Hou, John Nakayama, Jennifer MacDonald, Kathleen Lutz, Vicky Makker, Roisin E. O'Cearbhaill
Summary: This article reviews the applications of oral tyrosine kinase inhibitors (TKIs) in gynecologic malignancies and summarizes the common adverse events associated with these drugs and their management strategies. TKIs have the potential to improve response rates and provide durable responses in certain patients. However, drug-related toxicity requires careful attention and management.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Oncology
Michal Hlavac, Annika Dwucet, Richard Eric Kast, Jens Engelke, Mike-Andrew Westhoff, Markus D. Siegelin, Klaus-Michael Debatin, Christian Rainer Wirtz, Marc-Eric Halatsch, Georg Karpel-Massler
Article
Pharmacology & Pharmacy
Marc-Eric Halatsch, Richard Eric Kast, Annika Dwucet, Michal Hlavac, Tim Heiland, I. Mike-Andrew Westhoff, Klaus-Michael Debatin, Christian Rainer Wirtz, Markus David Siegelin, Georg Karpel-Massler
BRITISH JOURNAL OF PHARMACOLOGY
(2019)
Article
Clinical Neurology
Tim Heiland, Georg Karpel-Massler, Angelika Scheuerle, Christian-Rainer Wirtz, Marc-Eric Halatsch
WORLD NEUROSURGERY
(2020)
Article
Oncology
Maximilian Pruss, Annika Dwucet, Mine Tanriover, Michal Hlavac, Richard Eric Kast, Klaus-Michael Debatin, Christian Rainer Wirtz, Marc-Eric Halatsch, Markus David Siegelin, Mike-Andrew Westhoff, Georg Karpel-Massler
BRITISH JOURNAL OF CANCER
(2020)
Review
Oncology
Patricia Kattner, Hannah Strobel, Nika Khoshnevis, Michael Grunert, Stephan Bartholomae, Maximilian Pruss, Rahel Fitzel, Marc-Eric Halatsch, Katharina Schilberg, Markus D. Siegelin, Aurelia Peraud, Georg Karpel-Massler, Mike-Andrew Westhoff, Klaus-Michael Debatin
CANCER AND METASTASIS REVIEWS
(2019)
Article
Neurosciences
Richard E. Kast, Alex P. Michael, Iacopo Sardi, Terry C. Burns, Tim Heiland, Georg Karpel-Massler, Francois G. Kamar, Marc-Eric Halatsch
Article
Multidisciplinary Sciences
Karthika D. Selvasaravanan, Nicole Wiederspohn, Amina Hadzalic, Hannah Strobel, Christel Payer, Andrea Schuster, Georg Karpel-Massler, Markus D. Siegelin, Marc-Eric Halatsch, Klaus-Michael Debatin, Mike-Andrew Westhoff
SCIENTIFIC REPORTS
(2020)
Article
Clinical Neurology
Martin N. Stienen, Christian F. Freyschlag, Karl Schaller, Torstein Meling
ACTA NEUROCHIRURGICA
(2020)
Article
Clinical Neurology
R. E. Kast, T. C. Burns, M-E Halatsch
Summary: This paper presents a dexamethasone sparing regimen, SEC, to reduce glioblastoma related brain edema through repurposing old drugs. A pilot study is favored to determine if the three drug regimen of SEC can reduce corticosteroid use during glioblastoma treatment. The chosen drugs, spironolactone, ecallantide, and clotrimazole, have preclinical evidence of glioblastoma growth inhibition, in addition to their potential to reduce edema.
Article
Cell Biology
Richard E. Kast, Marc-Eric Halatsch, Rafael Rosell
Summary: The study developed a five-drug adjuvant regimen to enhance the growth inhibition of osimertinib and delay the development of resistance. While the preclinical data is strong, there remains uncertainty regarding potential discrepancies between preclinical data and clinical trial results, as well as the tolerability of the drugs when used together in humans.
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.
Article
Chemistry, Medicinal
Marc-Eric Halatsch, Annika Dwucet, Carl Julius Schmidt, Julius Muhlnickel, Tim Heiland, Katharina Zeiler, Markus D. Siegelin, Richard Eric Kast, Georg Karpel-Massler
Summary: The study found that CUSP9v3 has significant anti-proliferative and pro-apoptotic effects on various glioblastoma models. It also reduces cell migratory capacity and ability to form tumor spheres. Additionally, the combination with temozolomide did not enhance the anti-neoplastic activity of CUSP9v3 in vitro.
Article
Oncology
Richard E. Kast, Alex Alfieri, Hazem Assi, Terry C. Burns, Ashraf M. Elyamany, Maria Gonzalez-Cao, Georg Karpel-Massler, Christine Marosi, Michael E. Salacz, Iacopo Sardi, Pieter Van Vlierberghe, Mohamed S. Zaghloul, Marc-Eric Halatsch
Summary: This paper presents eight core attributes of cancer growth that need to be addressed for more effective treatment. It suggests that a regimen using multiple drugs will be necessary to counter the growth attributes of incurable cancer. The paper further shows how repurposed drugs can be used to block cancer cells' survival pathways and growth drives. It presents the principles of multidrug adjunctive cancer treatment (MDACT) and provides an example regimen using six repurposed drugs to interfere with common growth-driving elements in different types of cancer.
Article
Clinical Neurology
Daniel Schoni, Marc-Eric Halatsch, Alex Alfieri
Summary: The COVID-19 pandemic had a significant impact on the operations of the neurosurgical department. The reduction in operating room capacity resulted in fluctuations in the number of surgeries and outpatient visits, but there was no significant delay in urgent neurosurgical care.
INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT
(2022)
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.