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CANCER:

Glioblastoma

Related cancers:
10h
A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM]. (PubMed, BMC Neurol)
The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
Review • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation • MGMT expression
12h
Noscapine and Apoptosis in Breast and Other Cancers. (PubMed, Int J Mol Sci)
Gene expression was higher in tumor than in normal tissue, including the BAX expression levels in lung, ovary, endometrium, colon, stomach, and glioblastoma patients; BCL2L1 expression in endometrium, colon, and stomach patients; CASP8 gene expression levels in lung, endometrium, colon, stomach, and glioblastoma patients; RELA in colon, stomach, and glioblastoma patients; and NFKBIA in glioblastoma patients. It can be concluded that noscapine affected genes and proteins related to apoptosis in cancer cell lines and several types of cancer patients.
Review • Journal
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BCL2L1 (BCL2-like 1) • BAX (BCL2-associated X protein) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • NFKBIA (NFKB Inhibitor Alpha 2) • RELA (RELA Proto-Oncogene)
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BAX expression
12h
Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes. (PubMed, Int J Mol Sci)
This research highlights the critical function of SIRT3 in mitochondrial metabolism and its broader implications for cellular energetics. It also provides a comparative analysis of the proteome and acetylome across glioblastoma cell lines with opposing metabolic phenotypes.
Journal
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SIRT3 (Sirtuin 3)
12h
Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types. (PubMed, Int J Mol Sci)
EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.
Journal
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HSPA1A (Heat Shock Protein Family A (Hsp70) Member 1A)
12h
Repurposed Drugs Celecoxib and Fmoc-L-Leucine Alone and in Combination as Temozolomide-Resistant Antiglioma Agents-Comparative Studies on Normal and Immortalized Cell Lines, and on C. elegans. (PubMed, Int J Mol Sci)
Safety tests of repurposing drugs used in cancer therapy tested on C. elegans nematode indicated that CXB, FL, or their mixture at a concentration of up to 100 µM had no significant effect on the entire nematode organism up to 4th day of incubation. After a 7-day treatment, CXB significantly shortened the lifespan of C. elegans at 25-400 µM concentration and body length at 50-400 µM concentration.
Preclinical • Journal
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PTGS2 (Prostaglandin-Endoperoxide Synthase 2)
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PTGS2 expression
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temozolomide • celecoxib oral
14h
Bis-Indole Derivatives as Dual Nuclear Receptor 4A1 (NR4A1) and NR4A2 Ligands. (PubMed, Biomolecules)
The DIM-3,5 and DIM8-3,5 analogs were cytotoxic to U87 glioblastoma and RKO colon cancer cells and the DIM-3,5 compounds were more cytotoxic than the DIM8-3,5 compounds. These studies show that both DIM-3,5 and DIM8-3,5 compounds previously identified as NR4A1 ligands bind both NR4A1 and NR4A2 and are dual NR4A1/2 ligands.
Journal
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NR4A1 (Nuclear Receptor Subfamily 4 Group A Member 1) • NR4A2 (Nuclear Receptor Subfamily 4 Group A Member 2)
15h
Comprehensive Transcriptomic Profiling of Diverse Brain Tumor Types Uncovers Complex Structures of the Brain Tumor Microenvironment. (PubMed, Biomedicines)
Our results unveiled the distinct TME across brain tumor types and provided a transcriptomic landscape. Our findings may contribute to realizing future precision medicine, providing a basic rationale for the therapeutics of brain tumors.
Journal
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
16h
Treatment Strategies for Glioblastoma in the Elderly: What Should We Focus on Compared to Younger Patients. (PubMed, Cancers (Basel))
Furthermore, MGMT methylation seems to be associated with a longer PFS in elderly patients. Further investigations are required to confirm these findings, especially within prospective radiation therapy studies and molecular examinations.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
17h
Exploring Genetic Determinants: A Comprehensive Analysis of Serpin B Family SNPs and Prognosis in Glioblastoma Multiforme Patients. (PubMed, Cancers (Basel))
The high-risk group showed a significantly higher infiltration of M2 macrophages and activated mast cells. Our findings showed a significant role of the Serpin B family in GBM survival in the Jordanian population.
Journal
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SERPINB3 (Serpin family B member 3)
17h
Potential diagnostic and drug target markers in glioblastoma. (PubMed, Sci Rep)
We further performed computational docking analysis of potential drug candidate Nisin against GCSF, and the results were validated in vitro through cytotoxic activity assay using a human glioblastoma cell line SF-767 in a dose-dependent manner. Our comprehensive analysis reveals that GCSF augments glioma progression, and its blockade with anticancer bacteriocin peptide Nisin can potentially inhibit the growth and metastasis of GBM.
Journal
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CSF3R (Colony Stimulating Factor 3 Receptor) • STAT3 (Signal Transducer And Activator Of Transcription 3)
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IDH wild-type
17h
Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines. (PubMed, Sci Rep)
This distinct hypoxia response of IDH-mutant gliomas may contribute to its more favorable prognosis. Our transcriptomic studies provide a basis for future approaches to better understand the diversity of hypoxic niches in gliomas.
Preclinical • Journal
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SESN2 (Sestrin 2)
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IDH wild-type
24h
New P2 trial • Combination therapy
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lomustine • Fibromun (onfekafusp alfa)
1d
A Phase 1a/1b Study to Determine the Recommended Phase 2 Dose, of Tepotinib in Participants With MET Alterations and Brain Tumors (clinicaltrials.gov)
P1, N=60, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
Enrollment closed • Phase classification • Trial completion date • Trial primary completion date
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MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR T790M • MET exon 14 mutation • IDH wild-type
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Tagrisso (osimertinib) • Tepmetko (tepotinib)
1d
Predominance of MGMT promoter methylation among Pakistani glioblastoma patients. (PubMed, Mol Biol Rep)
This is the first comprehensive study highlighting a predominance of MGMT methylation in Pakistani GBM patients. Furthermore, our findings underscore the association of MGMT methylation with improved OS across diverse treatment modalities. Larger studies are imperative to validate our findings for better management of Pakistani GBM patients.
Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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MGMT promoter methylation
1d
CD13 expression affects glioma patient survival and influences key functions of human glioblastoma cell lines in vitro. (PubMed, BMC Cancer)
Bestatin treatment reduced proliferation, migration and colony formation of glioma cells in a CD13-dependent manner while apoptosis was increased. In summary, CD13 has an impact on glioma patient survival and is important for the main function of specific glioma cells.
Preclinical • Journal
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ANPEP (Alanyl Aminopeptidase, Membrane)
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ubenimex (DFP-14323)
1d
OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses. (PubMed, Cancer Lett)
Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.
Journal • Oncolytic virus • IO biomarker • Tumor cell
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule)
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CDKN2A deletion • CDKN2A mutation
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BS001
1d
NOP14 as a Potential Predictor of Adult-Type Diffuse Glioma Prognosis and Immunotherapy, is Related to Cell Migration, Proliferation, and CD8+T Cell Infiltration. (PubMed, Front Biosci (Landmark Ed))
NOP14 holds great promise as a candidate biomarker for detecting prognostic, molecular, and immune signatures of adult-type diffuse glioma.
Journal • IO biomarker
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CD8 (cluster of differentiation 8)
1d
WTAP regulates the production of reactive oxygen species, promotes malignant progression, and is closely related to the tumor microenvironment in glioblastoma. (PubMed, Aging (Albany NY))
Finally, based on functional enrichment analysis, we further performed immune-related analysis on WTAP. In conclusion, this study analyzed WTAP from three aspects, which provided new ideas for the treatment of GBM.
Journal
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CAT (Catalase) • SOD1 (Superoxide Dismutase 1) • WTAP (WT1 Associated Protein)
1d
Spatially Resolved Microglia/Macrophages in Recurrent Glioblastomas Overexpress Fatty Acid Metabolism and Phagocytic Genes. (PubMed, Curr Oncol)
Tumor-associated microglia/macrophages in recurrent GBM overexpress genes involved in fatty acid/lipid metabolism. Further investigation is needed to fully delineate the role of PLD phospholipases in GBM progression.
Journal
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GFAP (Glial Fibrillary Acidic Protein)
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IDH wild-type
1d
Predictive value of procollagen c-protease enhancer protein on the prognosis of glioma patients. (PubMed, Heliyon)
Additionally, PCOLCE may exert its roles via several immune-related biological processes or pathways, such as leukocyte migration, activation of T cells, adaptive immune response, neutrophil-mediated immunity, NF-κB, and TNF signaling pathways. In conclusion, PCOLCE may be a new immune-related gene and regulate tumor development through immunological pathways.
Journal
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CD4 (CD4 Molecule)
1d
Exploring the combined anti-cancer effects of sodium butyrate and celastrol in glioblastoma cell lines: a novel therapeutic approach. (PubMed, Med Oncol)
These findings indicate that SB and CEL may act through multiple mechanisms, including DNA repair inhibition, apoptosis induction, and autophagy modulation, to exert their anti-cancer effects in glioblastoma cells. This is the first study providing novel insights into the potential therapeutic effects of SB and CEL in glioblastoma.
Preclinical • Journal
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MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • CASP9 (Caspase 9)
2d
CAR2BRAIN: Intracranial Injection of NK-92/5.28.z Cells in Combination With Intravenous Ezabenlimab in Patients With Recurrent HER2-positive Glioblastoma (clinicaltrials.gov)
P1, N=42, Active, not recruiting, Johann Wolfgang Goethe University Hospital | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Jun 2026 | Trial primary completion date: Oct 2023 --> Dec 2025
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive
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ezabenlimab (BI 754091) • HER2 t-haNK
2d
Ivy 2020-10: AZD1390 in Recurrent and Newly Diagnosed WHO Grade 4 Glioma Patients (clinicaltrials.gov)
P1, N=37, Recruiting, Nader Sanai | Trial primary completion date: Jan 2024 --> Jul 2024
Trial primary completion date
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AZD1390
2d
Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients (clinicaltrials.gov)
P1, N=48, Active, not recruiting, Nader Sanai | Trial completion date: Jan 2024 --> Jan 2025
Trial completion date
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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CDKN2A deletion • CCND1 amplification • CDK4 amplification
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Kisqali (ribociclib)
2d
Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion (clinicaltrials.gov)
P1, N=15, Not yet recruiting, Nationwide Children's Hospital
New P1 trial
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ALK fusion • ROS1 fusion
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carboplatin • Lorbrena (lorlatinib) • cyclophosphamide
2d
LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients (clinicaltrials.gov)
P1, N=50, Recruiting, Nader Sanai | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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CDK4 amplification
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Verzenio (abemaciclib) • temuterkib (LY3214996)
3d
A dynamic study of VEGF-A siDOX-EVs trafficking through the in-vitro insert co-culture blood-brain barrier model by digital holographic microscopy. (PubMed, Front Oncol)
Moreover, our results indicated that the VEGF-A siDOX-EVs insert cytotoxic impact on the cells of the bottom of the culture plate. folate-conjugation on the surface of EVs improves their trafficking through the blood-brain barrier and by using digital holographic microscopy analysis, we could directly assess the morphometric changes of the blood-brain barrier cells for pharmacological purposes as an easy, label-free, and real-time analysis.
Preclinical • Journal
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VEGFA (Vascular endothelial growth factor A)
3d
Chronic hypoxia remodels the tumor microenvironment to support glioma stem cell growth. (PubMed, Acta Neuropathol Commun)
When controlled for genotype, the close association between glioma aggressiveness and patient age has very few proposed biological explanations. Our findings indicate that age-associated increases in cerebral vascular insufficiency and associated regional chronic cerebral hypoxia may contribute to this phenomenon.
Journal
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FGF1 (Fibroblast Growth Factor 1)
3d
Cyclophosphamide stimulates endoplasmic reticulum stress and induces apoptotic cell death in human glioblastoma cell lines. (PubMed, Rom J Morphol Embryol)
The ER stress signal pathway could be active in 4-HC-induced cell death. Further studies of ER-related stress mechanisms in anticancer treatment would be important for effective therapeutic strategies.
Preclinical • Journal
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CASP3 (Caspase 3) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • ATF6 (Activating Transcription Factor 6) • ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1)
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cyclophosphamide
3d
Study to Evaluate the Safety, Tolerability, Immunogenicity and Preliminary Efficacy of ITI-1001 In Patients With Newly Diagnosed Glioblastoma (GBM) (clinicaltrials.gov)
P1, N=10, Active, not recruiting, Immunomic Therapeutics, Inc. | Trial primary completion date: Jun 2025 --> Mar 2026 | Recruiting --> Active, not recruiting
Enrollment closed • Trial primary completion date
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CD8 (cluster of differentiation 8) • CD163 (CD163 Molecule) • FOXP3 (Forkhead Box P3)
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ITI-1001
3d
OU-SCC-PI-4G: PARP Inhibition for Gliomas (PI-4G or π4g) (clinicaltrials.gov)
P2, N=15, Terminated, University of Oklahoma | N=45 --> 15 | Trial completion date: Nov 2024 --> Feb 2024 | Active, not recruiting --> Terminated; Funder terminated funding.
Enrollment change • Trial completion date • Trial termination
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Myriad myChoice® CDx
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Zejula (niraparib)
3d
RiNG: Reirradiation and Niraparib in Patients With Recurrent Glioblastoma (clinicaltrials.gov)
P1, N=0, Withdrawn, University College, London | N=15 --> 0 | Trial completion date: Jun 2025 --> Oct 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: Jul 2024 --> Oct 2023
Enrollment change • Trial completion date • Trial withdrawal • Trial primary completion date
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Zejula (niraparib)
3d
Partial Brain RT, Temozolomide, Chloroquine, and TTF Therapy for the Treatment of Newly Diagnosed Glioblastoma (clinicaltrials.gov)
P1, N=2, Active, not recruiting, Barbara Ann Karmanos Cancer Institute | Recruiting --> Active, not recruiting | N=10 --> 2 | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2025
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
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temozolomide
3d
"Principle Test" for Isolation and Characterization of Circulating Cancer Cells (CTC)-CXCR4+. (clinicaltrials.gov)
P=N/A, N=47, Active, not recruiting, National Cancer Institute, Naples | Trial completion date: Jan 2024 --> Jan 2025
Trial completion date
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EPCAM (Epithelial cell adhesion molecule) • VIM (Vimentin)
|
nCounter® PanCancer Pathways Panel
3d
VB-111 in Surgically Accessible Recurrent/Progressive GBM (clinicaltrials.gov)
P2, N=15, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Mar 2024 --> Aug 2024
Trial primary completion date
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Avastin (bevacizumab) • ofranergene obadenovec (VB-111)
3d
Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway. (PubMed, Anticancer Drugs)
In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.
Journal
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BCL2 (B-cell CLL/lymphoma 2)
3d
Coactosin-Like Protein 1 (COTL1) Could Be an Immunological and Prognostic Biomarker: From Pan-Cancer Analysis to Low-Grade Glioma Validation. (PubMed, J Inflamm Res)
Furthermore, our findings confirmed a positive correlation between COTL1 expression, CD8, and PD-L1 in LGG, as well as an association of high COTL1 expression with decreased patient survival in LGG. Based on these compelling findings, COTL1 may hold significant clinical implications for the development of novel cancer therapies and serve as a potential target for tumors associated with immunotherapy in the future.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Pan tumor
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8)
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PD-L1 expression • HRD • CD8 expression
4d
New P2 trial
|
temozolomide
4d
New P2 trial • Tumor mutational burden • IO biomarker
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Tecentriq (atezolizumab) • tiragolumab (RG6058)
4d
Accurate DCE-MRI Measurement of Glioblastoma Using Point-of-care Portable Perfusion Phantom (clinicaltrials.gov)
P=N/A, N=12, Active, not recruiting, University of Alabama at Birmingham | Recruiting --> Active, not recruiting
Enrollment closed
4d
Harnessing the potential of nanoengineered siRNAs carriers for target responsive glioma therapy: Recent progress and future opportunities. (PubMed, Int J Biol Macromol)
The novel functionalized nanocarrier approach in conjunction with biological and chemical modification offers an intriguing potential to address challenges associated with the naked siRNA and efficiently silence STAT3, coffilin-1, EGFR, VEGF, SMO, MGMT, HAO-1, GPX-4, TfR, LDLR and galectin-1 genes in GBM tumor. This review highlights the nanoengineered siRNA carriers, their recent advancements, future perspectives, and strategies to overcome the systemic siRNA delivery challenges for glioma treatment.
Review • Journal
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EGFR (Epidermal growth factor receptor) • STAT3 (Signal Transducer And Activator Of Transcription 3) • LGALS1 (Galectin 1) • GPX4 (Glutathione Peroxidase 4)
4d
Diterpenoid honatisine overcomes temozolomide resistance in glioblastoma by inducing mitonuclear protein imbalance through disruption of TFAM-mediated mtDNA transcription. (PubMed, Phytomedicine)
In summary, our data provide new insights into the therapeutic mechanisms underlying honatisine's selective inducetion of apoptosis and its ability to overcome chemotherapy resistance in GBM. These actions are mediated through the disruption of mitochondrial proteostasis and function, achieved by the inhibition of TFAM-mediated mtDNA transcription. This study highlights honatisine's potential as a promising agent for glioblastoma therapy, underscoring the need for further exploration and investigation.
Journal
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TFAM (Transcription Factor A, Mitochondrial)
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temozolomide