^
23h
Multivariate analysis revealed that PD-L1 was the only independent factor that affected prognosis. PD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
|
PD-L1 expression • PD-L1 overexpression • CD8 positive
23h
These findings demonstrate the critical role of NEDD4-1 in regulating the redox imbalance in TMZ-resistant GBM cells via the degradation of PTEN and the upregulation of the AKT/NRF2/HO-1 signaling pathway. Targeting this regulatory axis may help eliminate TMZ-resistant glioblastoma.
Journal
|
PTEN (Phosphatase and tensin homolog)
|
PTEN expression
|
temozolomide
23h
MGMT promoter methylation has the greatest clinical significance in predicting responses to temozolomide (TMZ). Conversely, mismatch repair defects cause hypermutation phenotype predicting poor response to TMZ. Finally, we discussed liquid biopsies, which are promising diagnostic, prognostic, and predictive techniques, but further work is needed to implement these novel technologies in clinical practice.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase)
|
EGFR mutation • CDKN2A deletion • CDKN2A mutation • MGMT promoter methylation • TERT promoter mutation • TERT mutation
|
temozolomide
23h
Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.
Journal
|
CDH1 (Cadherin 1)
|
CDH1 expression
23h
We developed radiation-resistant and radiation-temozolomide-resistant GBM models to investigate the underlying mechanisms conferring TR. ALDH activity positively correlated with TGF-β-induced mesenchymal properties in TR GBM. CSCs and mesenchymal-like GBM cells targeted together by combining DSF and Galunisertib may be a good therapeutic strategy for recurrent GBM patients.
Journal
|
TGFB1 (Transforming Growth Factor Beta 1)
|
temozolomide • galunisertib (LY2157299) • disulfiram
23h
Journal
|
RHOA (Ras homolog family member A) • CDH5 (Cadherin 5)
23h
In addition, transwell assays demonstrated that NANOG regulates cancer cell migration through the SDF1/CXCR4 pathway. Altogether, our results uncover NANOG-CXCR4 as a novel pathway controlling cellular migration and support Nanog as a potential therapeutic target in the treatment of Nanog-dependent tumor progression.
Journal
|
CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12) • NANOG (Nanog Homeobox)
|
CXCR4 expression
24h
The effect of the anticancer activity of graphene-based complexes functionalised by the miRNA sequence was analysed using 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide salt (XTT) assays at the gene expression level. The results partly explain the mechanisms of miRNA deregulation stress, which is affected by graphene-based complexes together with the forced transport of mimic miR-124, miR-137 and antisense miR-21, -221 and -222 as an anticancer supportive therapy.
Journal
|
MIR21 (MicroRNA 21)
1d
The latter was required for the enhanced migration observed upon silencing of Par3 as anti-oxidants blocked the enhanced migration. These findings support the notion that Par3 exerts homeostatic redox control, which could limit the tumor cell-derived pool of oxygen radicals, and thereby the tumorigenicity of GBM.
Journal
|
CD133 • SOX2 • NES (Nestin) • GFAP (Glial Fibrillary Acidic Protein)
|
CD33 positive
1d
The intracranial GBM mouse model also demonstrated that the synergy between PP and TMZ could be achieved through down-regulating β-catenin and MGMT, which prolonged the survival time of tumor-bearing mice. Taken together, our data suggest that PP may serve as the prospect medicine to improve the chemotherapeutic effect on GBM, especially for chemoresistant to TMZ induced by MGMT overexpression.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT overexpression
|
temozolomide
1d
P1, N=42, Recruiting, Taiho Oncology, Inc. | Not yet recruiting --> Recruiting | N=142 --> 42
Clinical • Enrollment open • Enrollment change
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive
|
TAS2940
2d
Moreover, it lessened the apoptotic cell amount and enhanced the live-cell percentage in the flow cytometry and DAPI staining. As a result, thiamine may be beneficial nutritional support for individuals with a predisposition to neurodegenerative disorders due to its protective effect on glutamate cytotoxicity in glioblastoma cells by suppressing OS and ER stress.
Journal
|
ATF4 (Activating Transcription Factor 4) • CAT (Catalase) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
2d
Furthermore, we observed that GBM cells more frequently migrated along the residual RFs formed by preceding cells in microfluidic channels in comparison to those in the channels without RFs, suggesting that the infiltrative characteristics GBM could be attributed to RFs formed by the preceding cells in concert with chemoattractant cues. Altogether, we demonstrated that shedding membrane structures of GBM cells are maintained by FN-integrin α5β1 interaction and promoted their motility .
Journal
|
FN1 (Fibronectin 1)
2d
Clinical • Retrospective data • Review • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation
2d
Simultaneous THBS1 overexpression and MYH9 knockdown suppressed glioma cell invasion and migration. These data suggest that apatinib targets THBS1 in glioma cells, potentially via MYH9, to inhibit glioma cell malignancy and may provide novel targets for glioma therapy.
Preclinical • Journal
|
MYH9 (Myosin Heavy Chain 9)
|
THBS1 overexpression
|
AiTan (rivoceranib)
2d
Organizing pneumonitis is one of the fatal complications that has been reported with the use of temozolomide. Physicians should consider this as one of the differential diagnoses while treating acute respiratory distress in the setting of temozolomide use. Infection should be ruled out and high dose steroid therapy should be started as early as possible and is the key element to achieve medical response and decrease mortality in these patients.
Clinical • Review • Adverse events
|
CD4 (CD4 Molecule)
|
temozolomide
3d
New P1 trial
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
IDH2 mutation • ATRX mutation
|
Zejula (niraparib)
3d
The proposed approach obtained a high value of accuracy and other statistical parameters compared with other state-of-the-art machine learning classifiers. Therefore, the proposed framework can be utilised for designing other intervention strategies for the prediction of glioma cases and their grades.
Journal
|
IL6 (Interleukin 6) • TERT (Telomerase Reverse Transcriptase) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • CHI3L1 (Chitinase 3-like 1)
3d
CircCDC45 promoted the progression of GBM by mediating the miR-485-5p/CSF-1 axis, and circCDC45 might be a promising plasmatic biomarker for GBM diagnosis and treatment.
Journal
|
CSF1 (Colony stimulating factor 1)
|
CSF1 expression
3d
Furthermore, we observed that 4MU increases the levels of RHAMM inside the cell while decreases the nucleus/cytoplasm relation of p-ERK, associated with 4MU effects on cell proliferation and senescence induction. Overall, 4MU should be considered as a promising therapeutic alternative to improve the outcome of patients with GBM.
Journal
|
CD44
|
CD44 expression
3d
One base pair insertions identical to those seen in a previous model were found around the target sequences in Nf1, Pten, and Trp53, and additional deletions were found only in Pten. Considering that the histological characteristics were different from those seen in the previous model, our new model provides an additional research tool to investigate the early stages of glioblastoma development.
Preclinical • Journal
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • GFAP (Glial Fibrillary Acidic Protein)
3d
Mechanistically, circCD44 could regulate the expression of SMAD6 via sponging miR-326 and miR-330-5p involved in the progression of GBM. Thus, the LRRC4/SAM68/circCD44/miR-326/miR-330-5p/SMAD6 signaling axis could be a potential target for GBM treatment.
Journal
|
CD44 • KHDRBS1 (KH RNA Binding Domain Containing, Signal Transduction Associated 1)
|
CD44 expression
3d
Ribosome biogenesis emerged as a vital contender of possible therapeutic potential with BYSL, NIP7, NOLC1, PNO1 and RRS1 showing prognostic value. The online version contains supplementary material available at 10.1007/s13205-021-02987-2.
Journal
|
EGFR (Epidermal growth factor receptor) • TNFAIP3 (TNF Alpha Induced Protein 3) • ETS1 (ETS Proto-Oncogene 1) • TNFRSF1B (Tumor necrosis factor receptor superfamily member 1B)
3d
On multivariable linear regression analysis, IDH1 mutation (β = 0.308, p < 0.001) and peritumoral brain edema volume (β = -0.353, p < 0.001) were the two independent factors associated with the ALPS index. IDH1 wild-type gliomas and gliomas with larger peritumoral brain edema volumes were associated with a lower ALPS index, which may reflect impaired glymphatic function.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation
3d
Further, SERBP1 undergoes liquid-liquid phase separation, mediated by salt and RNA, and both RGG boxes are necessary for the efficient formation of condensed phases. Together, these results provide a foundation for understanding the molecular mechanisms of SERBP1 functions in physiological and pathological processes.
Journal
|
PAI1 (Plasminogen Activator Inhibitor 1)
3d
P1/2, N=38, Active, not recruiting, VBI Vaccines Inc. | Trial completion date: Jul 2021 --> Mar 2022 | Trial primary completion date: Oct 2020 --> Mar 2022
Clinical • Trial completion date • Trial primary completion date
|
MGMT (6-O-methylguanine-DNA methyltransferase) • IFNG (Interferon, gamma) • CSF2 (Colony stimulating factor 2)
|
VBI-1901
4d
P1, N=48, Recruiting, Nader Sanai | Trial completion date: Apr 2022 --> Nov 2022 | Trial primary completion date: Dec 2021 --> Jun 2022
Clinical • Trial completion date • Trial primary completion date
|
CDKN2A (Cyclin-dependent kinase inhibitor 2A) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
|
CDKN2A deletion • CCND1 amplification • CDK4 amplification
|
Kisqali (ribociclib)
5d
Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.
Journal • Oncolytic virus
|
SIRPA (Signal Regulatory Protein Alpha)
5d
Taken together, these observations suggest a distinct clinical presentation, brain location, and gene expression profile for BRAF-mutant tumors. Pending further study, this may prove useful in the stratification and management of GBM.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
EGFR mutation • BRAF mutation • IDH1 mutation
5d
Moreover, intracellular levels of reactive oxygen species were elevated especially when NCT503 and TMZ treatments were combined, and the synergistic effects could be partially negated by NAC, a classic scavenger of reactive oxygen species. Taken together, these results suggest that NCT503 may be a promising agent for augmenting TMZ efficacy in the treatment of GBM, especially in TMZ-resistant GBMs with high expression of MGMT.
Clinical • Journal • Epigenetic controller
|
MGMT (6-O-methylguanine-DNA methyltransferase) • PHGDH (Phosphoglycerate Dehydrogenase)
|
MGMT overexpression
|
temozolomide
5d
Diffuse invasion of malignant tumor cells into surrounding healthy brain is a characteristic feature of GBM that makes therapy challenging. Here, we describe methods to assess SULF2 expression in human tumor tissue and cell lines and how to relate this to tumor cell invasion.
Journal
|
SULF2 (Sulfatase 2)
5d
Furthermore, molecular modeling studies were employed to understand the binding mode of these acetate molecules to mTOR, Rapamycin-insensitive companion of mammalian target of rapamycin (Rictor), and HDAC-8 proteins. Thus in this study, we have identified the pivotal role of acetates in the modulation of mTOR complex, epigenetic genes and provide structural as well as functional insights that will help in future drug discovery against GBM cancer therapy.
Preclinical • Journal • Epigenetic controller
|
MIR155 (MicroRNA 155) • MIR17 (MicroRNA 17) • MIR223 (MicroRNA 223) • MIR15B (MicroRNA 15b)
|
miR-155 expression
6d
The initial three patients experienced no dose-limiting toxicity and exhibited clinical, as well as correlative laboratory, evidence of local CNS immune activation, including high concentrations of CXCL10 and CCL2 in the cerebrospinal fluid. This interim report supports the feasibility of generating HER2-specific CAR T cells for repeated dosing regimens and suggests that their repeated intra-CNS delivery might be well tolerated and activate a localized immune response in pediatric and young adult patients.
Clinical • Clinical Trial,Phase I • Journal • CAR T-Cell Therapy
|
HER-2 (Human epidermal growth factor receptor 2) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CCL2 (Chemokine (C-C motif) ligand 2) • TYK2 (Tyrosine Kinase 2)
6d
Depletion of FOSL1 in NF1-mutant human BTSCs and Kras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature and reduction in stem cell properties and in vivo tumorigenic potential. Our data demonstrate that FOSL1 controls GBM plasticity and aggressiveness in response to NF1 alterations.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • NF1 (Neurofibromin 1)
|
KRAS mutation
6d
The optimized rationally designed FAP-targeting PET tracer, &lsqb;Ga]Ga-Alb-FAPtp-01, with albumin-binding capability demonstrated prominent tumor uptake over time. The mean standard uptake value (SUV) and the tumor/muscle (T/M) ratio were as high as 1.775 ± 0.179 SUV and T/M = 5.9, 1.533 ± 0.222 SUV and T/M = 6.7, and 1.425 ± 0.204 SUV and T/M = 9.5, respectively, at 1, 2, and 3 h. Its improved tumor uptake and pharmacokinetics suggest that the &lsqb;Ga]Ga-Alb-FAPtp-01 tracer can noninvasively detect FAP activation in vivo, permitting a precise definition of its roles in tumors of different stages and yielding insights regarding FAP-targeted radiotherapeutic strategies at the molecular level.
Journal
|
FAP (Fibroblast activation protein, alpha)
6d
Regarding MRI postcontrast non-enhanced tumors, predominantly low grade gliomas (LGG), aggressive oncotherapy are reluctant to use but they are prone to repeat surgeries. Decision making issues are age, clinical patient status, histologic and genetic tumor characteristics, residual tumor volume, published guidelines for brain tumor treatment, and patient´s willing. Generally, hyposignal on the T1 postcontrast scans strictly relate to the better prognosis, even in HGG.
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation
6d
Our results bring new evidence that GBM associated FAP+ stromal cell promote angiogenesis by changing the balance between proangiogenic and antiangiogenic mediators and thus they may contribute to glioblastoma progression. Acknowledgement: Supported by Progres Q28/1LFUK and grant LM2015064 of the EATRIS-CZ and the Center for Tumor Ecology (CZ.02.1.01/0.0/0.0/16_019/0000785).
FAP (Fibroblast activation protein, alpha) • ENG (Endoglin)
|
FAP expression
6d
This is the first study to show that ascorbate levels were reduced in high-grade gliomas compared to low-grade. Some members of the hypoxic pathway were associated with ascorbate levels. The overall hypoxic pathway score did not significantly correlate with ascorbate and increased numbers of samples are required to confirm any associations.
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • CA9 (Carbonic anhydrase 9)
|
IDH1 mutation • HIF1A expression
6d
In summary, we optimized the Pi-ATAC method in a mouse GBM model to characterize the chromatin openness changes in GAMs and cancer cells in response to hypoxic stress. Further validation of these results will provide the potential to identify novel markers for GAMs/glioma interactions in hypoxic GBMs and develop novel therapeutic targets.
HIF1A (Hypoxia inducible factor 1, alpha subunit) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M)
6d
We have successfully established a 3D spheroid model to study the role of mesenchymal cells in GBM microenvironment. Our results indicate that mesenchymal cells may influence the infiltration of T cells and modulate their phenotype. Support: Project was financed by the Center for Tumor Ecology (CZ.02.1.01/0.0/0.0/16_019/0000785).
PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • IL2 (Interleukin 2) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD69 (CD69 Molecule) • NES (Nestin)
6d
The most studied, AS1411, had been in clinical trials... GQs as anti-proliferative crypto-aptamers with moderate activity due to restricted functioning of apparent GQ-binding proteins could be applied toward real glioma PCC_SSP. Variety of effects reflects glioma inter-tumor heterogeneity.Research was funded by Ministry of Education and Science of Russia, grant number № 075-15-2020-809 (13.1902.21.0030) and by Russian Foundation for Basic Research, grants number №18-29-01047
Preclinical
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
QN-165
6d
7 gain, we found that combined inhibition of both EGFR and PDGFRA using a variety of FDA-approved EGFR-targeted agents (Erlotinib, Gefitinib, Dacomitinib, Neratinib, and Osimertinib) and Crenolanib, respectively, leads to synergistic cytotoxicity in vitro. We show that combined inhibition of EGFR and PDGFRA exerts synergistic cytotoxicity in GBM and prevents resistance pathways that emerge during single-agent targeted therapy against these receptor tyrosine kinases. These pathways are targetable with FDA-approved agents that could be used in patients with GBM with Chr. 7 gain.
Clinical • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PDGFA (Platelet Derived Growth Factor Subunit A)
|
EGFR amplification
|
erlotinib • Tagrisso (osimertinib) • gefitinib • Nerlynx (neratinib) • crenolanib besylate (ARO-002) • Vizimpro (dacomitinib)
6d
These data demonstrate that, unlike CD95, CD95L is not expressed in cultured human GIC and that CD95-CD95L interactions are not required for tumor-promoting CD95 signaling. Although CD95 KO is detrimental for S-24 GIC in vitro, CD95 KO alone does not affect survival in S-24 human GIC xenograft-bearing mice.
FAS (Fas cell surface death receptor)
6d
Our data demonstrate that CAIX inhibition can effectively inhibit invasion in malignant glioma cells independent from oxygenation status, however the effects are significantly influenced by cell type specific biological features.
CA9 (Carbonic anhydrase 9)
|
CA9 expression
6d
We demonstrated the involvement of glioma-derived CHI3L1 in the growth of experimental human gliomas in an orthotopic xenograft model. We modelled CHI3L1 as a biomarker as tumour-derived human CHI3L1 is detectable in mouse blood. Our findings suggest that the depletion of CHI3L1 in glioma cells results in higher number of non-capillary blood vessels present in the tumour.
Preclinical
|
CHI3L1 (Chitinase 3-like 1)
6d
Patient resistance to the current standard of care, temozolomide and radiotherapy, is common and highlights the need to discover more effective treatment strategies. Collectively, these data demonstrate that CYC065 and THZ1 display high anti-cancer activity in primary and recurrent GBM and provide scientific rationale for the further development of CDK inhibitors to potentiate their clinical utilization in the future.
Preclinical
|
MCL1 (Myeloid cell leukemia 1) • CD133 • CD44 • CDK7 (Cyclin Dependent Kinase 7) • CDK9 (Cyclin Dependent Kinase 9)
|
temozolomide • fadraciclib (CYC065)
6d
A local glue containing UII may trap GB cells and remodel the tumor microenvironment responsible for survival and cognitive improvements, providing new option in the therapeutic arsenal of GB.
Preclinical
|
PODXL (Podocalyxin) • GFAP (Glial Fibrillary Acidic Protein)
6d
Our results show that high AR mRNA expression in GBM exhibits different effects on patients' survival depending on their sex, despite common occurrence of high AR expression and CN changes in males and females. The reasons for potential protective influence of AR in males remain unclear and require further investigations.
Clinical
|
AR (Androgen receptor)
|
AR expression
6d
The EF-14 study has shown that the addition of TTFields to temozolomide chemotherapy in patients with newly diagnosed GBM significantly improved overall survival (OS) and progression-free survival (PFS) without additional adverse events, apart from mild to moderate skin irritations (Stupp et al., JAMA 2017)... Taken together, our data provided the outcomes of using TTFields together with chemotherapy in the treatment of recurrent and newly diagnosed GBM in our department. Therapy with TTFields has been showing to provide significant clinical benefit for GBM patients.
Retrospective data
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
temozolomide
6d
To investigate which inhibitors against the Hippo-pathway were the most efficient, we performed a cytotoxic assay: we treated all the three cell lines with different inhibitors such as Verteporfin (VP), Cytochalasin D (CIT), Latrunculin A (LAT), Dobutamine (DOB) and Y27632. Afterwards, we performed a treatment using Doxorubicin (DOX) combined with the inhibitors, evaluating its cytotoxic effect on our cell lines, through cell viability experiments... Our results show that nuclear YAP is present in all tumor lines, thus confirming that this molecular pathway is functioning in GBM lines. Nuclear YAP is more highly expressed after DOX administration. Moreover, the combined treatment (DOX with Hippo-pathway inhibitors) reduces both cell proliferation and viability, and increases the rate of apoptosis.
Preclinical
|
YAP1 (Yes associated protein 1)
|
doxorubicin hydrochloride • Visudyne (verteporfin)
6d
We showed that glioblastoma cells upon transfection with recombinant DNA, that contains a fragment of CD133, mainly have a membrane localization of this marker. It was observed that CD133+ cells are more stable to external influence that can be a proof of the fact that CD133 is charactered for glioblastoma stem cells. We tested the effect of an GQ bi-(AID-1-T) and its combination with BDNF and showed that BDNF is necessary for blocking proliferation of glioblastoma cells.
CD133 • BDNF (Brain Derived Neurotrophic Factor)
|
CD133 expression
6d
GCL, PDCL and PT display heterogenic antigen surface expression with high variability within each group, thereby complicating clinical translation of in vitro results obtained using cell lines. This aspect should be taken into account in GBM target antigen research.
Preclinical • CAR T-Cell Therapy • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • CD133 • CD70 • CSPG4 (Chondroitin Sulfate Proteoglycan 4) • IL13RA2 (Interleukin 13 Receptor Subunit Alpha 2)
|
HER-2 expression • CD70 expression • CD133 expression • EGFRvIII expression
6d
This study demonstrates that CDKN2A deletion is associated with VTE in glioblastoma patients. Therefore, CDKN2A mutational status may be a promising predictor to identify patients with glioblastoma at high risk of VTE, who may benefit from thromboprophylaxis.
Clinical
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NOTCH1 (Notch 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • BRAF mutation • PIK3CA mutation • PTEN mutation • CDKN2A deletion • CDKN2A mutation • BRAF amplification
6d
TTFields in addition to temozolomide (TMZ) after radiochemotherapy according to Stupp significantly increased progression-free survival (PFS), overall survival (OS) and long-term survival rates in patients with newly diagnosed glioblastoma (GBM) in the multicenter phase 3, EF-14 trial...However, after three cycles, the unresected tumor progressed, TMZ was exchanged by procarbazine/CCNU and TTFields therapy was initiated... In the presented case, the combination of TTFields and CCNU was feasible and safe in progressive GBM. The patient showed radiological response and local tumor regression under the combination therapy, whereas the tumor had previously progressed under chemotherapy alone. In conclusion, the addition of TTFields to chemotherapy is a valuable treatment option to improve clinical and radiological outcome of patients with progressive GBM.
Clinical
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide • Matulane (procarbazine hydrochloride)
6d
Older patient's age, prolonged time between surgery and RT starting, male sex, negative IDH1/2 and MGMT, progression on the first MRI were associated with poor overall survival in glioblastoma patients. Our results suggested additional clinical, radiomics and molecular-genetic data should be added to improve the overall survival prediction. The results have been obtained under the support of the RFBR grant 18-29-01054
Clinical
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
6d
Conventional therapies, such as maximal extension of surgery followed by radiotherapy (RT) and chemotherapy with Temozolomide (TMZ) have not resulted in major improvements in terms of patients' outcome, overall survival (OS) still remaining poor...Thus, PsP seems not to be a marker of responsiveness to common treatment. Further data are needed to validate our results.
Retrospective data
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide
6d
Once GBM progresses after SOC, lomustine is the standard second-line treatment, while rechallenge with TMZ may be employed in selected patients with methylated promoter of MGMT, and bevacizumab is reserved for patients with extensive edema and need for steroids. To our knowledge, this is the first report of a recurrent GBM with a significant and long-lasting neuroradiological response following a combined treatment with TTFields, Depatux-M, and intensified schedule of TMZ. A synergistic effect of TTFields with compounds interfering with the microtubular system should be further investigated.
Clinical
|
EGFR (Epidermal growth factor receptor) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
EGFR amplification
|
Avastin (bevacizumab) • temozolomide • lomustine • depatuxizumab mafodotin (ABT-414)
6d
Patients receiving radiotherapy to 60 Gray with concomitant and adjuvant temozolomide at primary diagnosis had best outcome with median OS of 16.1 months and 9.3% were alive at 5 years...On Scheffé's post-hoc analyses chemotherapy alone and combined with bevacizumab were superior at second recurrence (p=0.008 and p=0.042, respectively) and chemotherapy combined with bevacizumab was superior at third recurrence (p=0.043), compared to no antineoplastic treatment... Recurrence treatment differed between the two institutions but there was no difference in OS. Our findings underline the lack of standard therapy upon GBM recurrence and the urgent need for novel therapeutic strategies.
Clinical
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
Avastin (bevacizumab) • temozolomide
6d
Despite being retrospective study and a few pts were treated with LM, there were no differences neither in PFS nor in OS in pts treated with LM vs FM at first or second line. Higher G1-2 thrombocytopenia was shown in the FM group probably due to a higher number of hematology samples collected.
Clinical
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
lomustine • Muphoran (fotemustine)
6d
In preclinical studies, SEL showed synergy with radiation, temozolomide and lomustine. Additional or modified arms to explore safety and efficacy of combinations with bevacizumab and/or Tumor Treating Fields are being considered. (Clinical trial identifier: NCT04421378)
P1 data • P2 data • Combination therapy • IO biomarker
|
XPO1 (Exportin 1)
|
Avastin (bevacizumab) • temozolomide • Xpovio (selinexor) • lomustine
6d
The EANO guidelines recommend >70-year-old patients with good performance status to undergo maximal safe resection followed by hypofractionated (40 Gy in 15 fractions, i.e. RT40/15) radiotherapy with or without concurrent and adjuvant Temozolomide (TMZ), depending on MGMT promoter methylation... When appropriate and safe, a subgroup of elderly glioblastoma patients may benefit from more aggressive surgical and oncological management. The proposed EGSS and EGOS scores takes into account important prognostic factors to help guide which patients should receive such treatment.
Clinical
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
temozolomide
6d
Gyriform infiltration is a specific imaging marker of molecular glioblastomas and IDH wildtype pTERT mutant diffuse gliomas.
Clinical
|
TERT (Telomerase Reverse Transcriptase)
|
TERT mutation
6d
WSTF is an important factor in both MGMT de- and proficient GBM cell lines for response against TMZ chemotherapy. The loss of WSTF leads to a significantly increased TMZ sensitivity in clinically relevant concentrations for all the studied cell lines. Ongoing studies are investigating the underlying mechanisms and potential alterations in the DDR pathway caused by WSTF loss.
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide
6d
Material and We report our experience from 2016 to 2018 in treating patients with radiotherapy and concomitant Nimotuzumab/Vinorelbine, as already published for DIPG's patients (DOI10.1007/s11060-014-1428-z). The molecular and phenotypic pattern of DMG allows to include patients in clinical trials/registry shared with patients suffering from DIPG. Our knowledge is still limited about this entity; new insights into molecular profile should help us to study new drugs directed against the effects of the H3K27M mutations and to define new diagnostic/prognostic approach as liquid biopsy able to correlate treatments and prognosis
Clinical
|
TP53 (Tumor protein P53) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
|
TP53 mutation
|
vinorelbine tartrate • TheraCIM (nimotuzumab)
6d
Our study thus identifies several crucial differences between male and female glioma, which could be validated further. It also highlights that molecular studies without consideration of gender can obscure critical elements of biology and emphasizes the importance of parallel but separate analyses of male and female glioma.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • KDM6A (Lysine Demethylase 6A) • ANKRD1 (Ankyrin Repeat Domain 1) • DDX3X (DEAD-Box Helicase 3 X-Linked)
6d
We retrospectively reviewed the data of 382 patients with GBM who underwent surgical resection and temozolomide-based chemoradiotherapy...The MGMT-methylation status may further stratify patients who could benefit from WVRT. Further prospective evaluation of WVRT in GBM is warranted.
Clinical • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT unmethylation
|
temozolomide
6d
Moreover, analogously to those affecting older children, they are IDH1-2 and H3.3K27M (when located outside midline) not-mutated while BRAFV600E mutation is typical of gangliogliomas/gangliocytomas and pleomorphic xanthoastrocytomas. High-grade astrocytomas have a more favorable prognosis compared with the same lesions occurring later in life while ependymomas have a poorer outcome.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
BRAF V600E • BRAF V600 • H3.3K27M
6d
These data show that PREX1 links aberrant PI 3-kinase signaling to Lgl1 phosphorylation in glioblastoma, but that TIAM1 is also to fill this role in a subset of patients. This redundancy between PREX1 and TIAM1 is only partial, as motility was impaired in PREX1 knockout cells from both patients.
Journal
|
PTEN (Phosphatase and tensin homolog) • TIAM1 (TIAM Rac1 Associated GEF 1)
7d
Genetic or pharmacological targeting of YY1-CDK9 complex elicited RNA m6A modification-dependent interferon responses, reduced regulatory T cell infiltration, and augmented efficacy of immune checkpoint therapy in glioblastoma. Collectively, these results suggest that YY1-CDK9 transcription elongation complex defines a targetable cell state with active transcription, suppressed interferon responses, and immunotherapy resistance in glioblastoma.
Journal • IO biomarker
|
CDK9 (Cyclin Dependent Kinase 9)
7d
P1/2, N=65, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
Clinical • Trial completion date • Trial primary completion date
|
TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • GZMB (Granzyme B)
|
temozolomide
8d
In this review, we provide a gene expression profile of these channels in different types of cancers and decipher their roles, in particular the roles of two-pore channel 2 (TPC2) and TRPML1 in melanocytes and melanoma. We specifically discuss the signaling cascades regulating MITF and the relationship between endolysosomal cation channels, MAPK, canonical Wnt/GSK3 pathways and MITF.
Review • Journal
|
MITF (Melanocyte Inducing Transcription Factor)
8d
The findings of this study indicate that by using SWCNT, more drugs can reach the target cells. This method reduces the total amount of required medication and shows a more beneficial therapeutic effect.
Preclinical • Journal
|
CASP3 (Caspase 3)
|
atorvastatin • methamphetamine
8d
We further proved that activation of autophagy leads to a decrease of Smurf1 and the inhibition of the PI3K/Akt signaling pathway in glioblastoma cells. Our results suggest that enhancement of autophagic degradation of Smurf1 may be a potential approach to treating glioblastoma.
Journal
|
TGFB1 (Transforming Growth Factor Beta 1)
8d
To refine treatment, we applied a com bined approach based on ADI and the cyclin-dependent kinase inhibitors (CDKi) abemaciclib (CDK4 / 6), and dinaciclib (CDK1 / 2/5/9). This study highlights the strong antitumoral potential of a combined arginine deprivation and CDK inhibition via complex effects on mitochondrial and ER dysfunction, invasiveness as well as DNA-dam age response. In particular, sequential administration of CDKi followed by SpyADI appears to be most effective. This provides a good starting point for further in vitro and in vivo proof-of-concept studies to move forward with this strategy.
CDK4 (Cyclin-dependent kinase 4) • RAD51 (RAD51 Homolog A) • CDK1 (Cyclin-dependent kinase 1) • XRCC1 (X-Ray Repair Cross Complementing 1)
|
Verzenio (abemaciclib) • dinaciclib (MK-7965)
9d
We cannot draw strong conclusions about use of frozen tissue vs formalin-fixed paraffin-embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and PSQ at CpG sites ranging from 72 to 95. A cutoff threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in 2 of the 3 good-quality studies. About 190 studies were identified presenting HRs from survival analysis in patients in which MGMT methylation was measured by 1 technique only.
Retrospective data • Review • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
temozolomide
9d
These data provide deeper insights into the complex EGFRvIII biology and provide new insights for targeting EGFRvIII mutated tumours.
Journal
|
EGFR (Epidermal growth factor receptor) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
|
EGFR mutation • EGFR amplification • EGFR expression • MDM2 amplification • CDK4 amplification • EGFRvIII mutation • EGFRvIII expression
9d
This study established and verified an ARG risk model, which can serve as an independent predictor for prognosis, reflect on the strength of the immune response and predict the potential drugs in glioma. Our findings offer new understandings of ARG molecular mechanism and promising therapeutic targets for glioma treatment.
Journal
|
BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • ATG5 (Autophagy Related 5) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase)
9d
In second-line arms, patients with EGFR-amplified recurrent WHO grade III/IV glioma received Depatux-M plus chemotherapy (temozolomide), or Depatux-M alone regardless of EGFR status. The 6-month PFS estimate was 25.6% (95% confidence interval &lsqb;CI] 11.4-42.6) and median PFS was 2.1 months (95% CI 1.9-3.9) with second-line Depatux-M plus chemotherapy in the EGFR-amplified subgroup. This study showed acceptable safety profile of Depatux-M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma.
Clinical • P1/2 data • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR amplification
|
temozolomide • depatuxizumab mafodotin (ABT-414)
9d
Temozolomide-induced changes in cell mass distributions predict patient overall survival similarly to O-methylguanine-DNA methyltransferase (MGMT) promoter methylation and may aid in predictions in gliomas with mismatch-repair variants of unknown significance, where MGMT is not predictive. Our findings suggest cell mass is a promising functional biomarker for cancers and drugs that lack genomic biomarkers.
Clinical • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide
10d
All patients were treated with temozolomide-based chemoradiotherapy after surgery...Several sex-based molecular subtypes of glioblastoma with different response to current treatment may exist explaining conflicting survival results in different patient cohorts. Further research on sex-based differences in IDHwt glioblastoma patients is needed.
Retrospective data • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide
10d
The present study suggests that adult cAA constitute a group of gliomas with relatively higher rate of IDH-1 mutations and prognosis similar to supratentorial AA. The present study is the first to systematically compare cAA and supratentorial AA with respect to their genetic characteristics and suggests that both groups show a similar survival prognosis.
Clinical • Review • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation
10d
Glioblastoma (GBM) is an aggressive malignant brain tumor; surgery, radiation, and temozolomide still remain the main treatments...Furthermore, E2F1 suppression inhibited or delayed GBM cell differentiation by maintaining a reasonable proportion of CD133+ cells when grown at differentiation condition. Therefore, E2F1 proved to be an interesting molecular target for therapeutic intervention in U87MG cells.
Journal
|
CD133 • E2F1 (E2F transcription factor 1)
|
temozolomide
10d
Because various inhibitory immune checkpoints can regulate anti-tumoral immune responses, the single-cell sequencing of the cells residing in the tumor microenvironment can provide valuable insights into the expression patterns of inhibitory immune checkpoints in the tumor micromovement. Thus, administrating immune checkpoint inhibitors based on the data from the single-cell sequencing of these cells can increase patients' response rates, decrease the risk of immune-related adverse events development, prevent immune-resistance development, and reduce the risk of tumor recurrence.
Review • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8)
|
PD-L1 overexpression
10d
Mesenchymal differentiation is also observed in the negative immune response clusters. High enrichment status of macrophages in negative immune response clusters is independently validated by analyzing scRNA-seq data from eight high-grade gliomas, revealing that negative immune response samples comprised 46.63 to 55.12% of macrophages, whereas positive immune response samples comprised only 1.70 to 8.12%, with IHC staining of samples from six short-term and six long-term survivors of GBMs confirming the results.
Journal
|
CD8 (cluster of differentiation 8)
10d
Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.
Journal
|
TP53 (Tumor protein P53) • NF1 (Neurofibromin 1)
|
TP53 mutation • NF1 mutation
10d
Furthermore, Spi significantly upregulated miR-34a and miR-125b that have a key role in the progression of PI3K/AKT/mTOR pathway. This is the first in vivo report on the chemo-preventive effect of Spi against glioblastoma, suggesting its potential use in the chemoprevention of this cancer and the antiglioma molecular mechanism of Spi.
Preclinical • Journal
|
mTOR (Mechanistic target of rapamycin kinase) • MIR34A (MicroRNA 34a-5p)
10d
miR-411 participated in the development of glioblastoma and function as a prognostic biomarker. miR-411 functions as a tumor suppressor, which provides a novel potential therapeutic target of glioblastoma.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • STAT3 (Signal Transducer And Activator Of Transcription 3)
10d
Our findings suggest that BRCA1 & 2 can be regarded as poor prognostic factors in patients with glioma, with greater significance in LGG. In the future, more in-depth experiments will enable us to elucidate the mechanism of gliomagenesis and identify potential gene therapy targets.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
|
BRCA1 expression • BRCA2 expression
12d
These findings highlight that AT/RTs, potentially paradigmatic for other pediatric tumors with a low mutational load, present a variety of highly immunogenic HLA class I and class II peptides from canonical as well as non-canonical protein sources. Inclusion of such cryptic peptides into therapeutic vaccines would enable an optimized mapping of the tumor cell surface, thereby reducing the likelihood of immune evasion.
Journal • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • SMARCB1
|
SMARCB1 deletion
12d
Our results demonstrate that combining an NKAB antibody with effector cells expressing an activating NKAR receptor represents a powerful and versatile approach to simultaneously enhance tumor antigen-specific as well as NKG2D-CAR and natural NKG2D-mediated cytotoxicity, which may be particularly useful to target tumors with heterogeneous target antigen expression.
Journal • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • NKG2D (killer cell lectin like receptor K1)
|
HER-2 positive • HER-2 expression
13d
Furthermore, TERT silencing altered the hsa-miR-29b-3p expression, a microRNA involved in the antidepressant effects of ketamine in animal models, and which is considered as a potential biomarker for neurological diseases. We found that after a 50 % of reduction of the TERT gene, the expression of ARG1 (Arginase 1) was upregulated, whereas NES (Nestin), GLUL (Glutamate-Ammonia Ligase), CREB1 (CAMP Responsive Element Binding Protein 1) and the hsa-miR-29b-3p microRNA were downregulated (P value <0.05). On the other hand, the bioinformatic analysis showed that hsa-miR-29b regulates genes associated with the collagens family and involved in the extracellular matrix organization and growth factor binding. The most significant pathway associated to target genes was focal adhesion.
TERT (Telomerase Reverse Transcriptase) • CREB1 (CAMP Responsive Element Binding Protein 1) • NES (Nestin)
|
ketamine
13d
Furthermore, TERT silencing altered the hsa-miR-29b-3p expression, a microRNA involved in the antidepressant effects of ketamine in animal models, and which is considered as a potential biomarker for neurological diseases. We found that after a 50 % of reduction of the TERT gene, the expression of ARG1 (Arginase 1) was upregulated, whereas NES (Nestin), GLUL (Glutamate-Ammonia Ligase), CREB1 (CAMP Responsive Element Binding Protein 1) and the hsa-miR-29b-3p microRNA were downregulated (P value <0.05). On the other hand, the bioinformatic analysis showed that hsa-miR-29b regulates genes associated with the collagens family and involved in the extracellular matrix organization and growth factor binding. The most significant pathway associated to target genes was focal adhesion.
TERT (Telomerase Reverse Transcriptase) • CREB1 (CAMP Responsive Element Binding Protein 1) • NES (Nestin)
|
ketamine
13d
These analyses were adjusted for age, Karnofsky performance status score, tumor volume, extent of resection, IDH1/2 tumor mutation, tumor MGMT promoter methylation, temozolomide and radiotherapy initiation, and maximum blood glucose level. Lower survival, steroid dependency, and higher infection rate in glioblastoma patients associated with higher dexamethasone administration in the initial 3 postoperative weeks. Nearly half of the glioblastoma patients are lymphopenic preoperatively and up to 1 month postoperatively.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
temozolomide • dexamethasone
13d
Screening of 107 FDA-approved anti-cancer drugs identified nine compounds with potent activity against IDHmt gliomas, including three compounds with favorable pharmacokinetic characteristics for CNS penetration: teniposide, omacetaxine mepesuccinate, and marizomib. Our twelve IDH-mutant cell cultures show high similarity to the parental tissues and offer a unique tool to study the biology and drug sensitivities of high-grade IDHmt gliomas in vitro. Our drug screening studies reveal lack of sensitivity to IDHmt inhibitors, but sensitivity to a set of nine available anti-cancer agents.
Preclinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
|
IDH1 mutation • CDKN2A deletion
|
Synribo (omacetaxine mepesuccinate) • Vumon (teniposide) • marizomib (NPI-0052)
13d
The delineation of different survival groups in the training and evaluation sets based on an interaction between chronological age and blood immune characteristics suggests that common host immune factors among different glioma types may impact survival. The ability of DNA methylation-based markers of immune status to capture diverse, clinically relevant information may facilitate non-invasive personalized patient evaluation in the neuro-oncology clinic.
Journal
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
13d
Reagents, processing protocols, and downstream analyses were thoroughly validated and optimized to resolve the following populations: T cells (CD4, CD8, CD3), B cells (B220), NK cells (NK1.1), neutrophils (Ly6G), classical and non-classical monocytes (Ly6c, CD43), macrophages (F4/80, CD11b), microglia (CD45-lo, CD11b), and dendritic cells (DCs) (CD11c, MHC class II). In addition, this panel leaves Alexa Fluor 488/FITC open for the inclusion of fluorescent reporters or congenic marker staining.
Preclinical • Journal
|
CD8 (cluster of differentiation 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ITGAM (Integrin, alpha M)
14d
Preclinical
|
TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)
14d
FASN (Fatty acid synthase)
14d
In addition, the miR-340a inhibitor suppressed the role of circNF1 siRNA silencing in cell proliferation. Therefore, circNF1 siRNA silencing may inhibit GBM cell proliferation by promoting the maturation of miR-340.
Journal
|
MIR340 (MicroRNA 340)
14d
Our study established and validated a seven-gene signature comprising METTL3, COL18A1, NASP, PHLPP2, TIMP1, U2AF2, and VEGFA, with a good capability for predicting glioma survival, which may guide therapeutic customization and clinical decision-making. These genes were identified to influence 81 anticancer drug responses, which further contributes to the early phase clinical trials of drug development.
Clinical • Journal
|
DLL3 (Delta Like Canonical Notch Ligand 3) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • NOTCH3 (Notch Receptor 3) • HES1 • IGF2BP2 (Insulin Like Growth Factor 2 MRNA Binding Protein 2) • METTL3 (Methyltransferase Like 3)
14d
Further research investigating modulation of the ACE1/ATII/ATR and ACE2/Ang(1-7)/MasR axes with RAS inhibitors may lead to novel treatment of CNS tumors and degenerative diseases. The aim of this review article is to discuss and highlight experimental and epidemiological evidence for the role of the RAS, its bypass loops and convergent signaling pathways in the pathogenesis of CNS tumors and degenerative diseases, to direct research that may lead to the development of novel therapy.
Review • Journal
|
POU5F1 (POU Class 5 Homeobox 1) • SOX2 • CTSS (Cathepsin S)
14d
By immunohistochemistry, IL-1β expression was seen on TAMs, especially in perinecrotic areas. These results suggest that IL-1β might be a useful target molecule for anti-glioblastoma therapy.
Journal
|
IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IL1B (Interleukin 1, beta)
14d
We have engineered the VEGF nanotrapper, a cargo system that allows cellular uptake of bevacizumab and inhibits VEGF secretion required for angiogenesis activation and development. Here, we show the remarkable therapeutic efficacy of this nanocargo in reducing vascularization and tumor cell mass of GBM in vitro and in vivo cancer models.
Journal
|
VEGFA (Vascular endothelial growth factor A)
|
Avastin (bevacizumab)
14d
P2, N=74, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=310 --> 74
Clinical • Enrollment closed • Enrollment change
|
PD-L1 (Programmed death ligand 1) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
Keytruda (pembrolizumab) • temozolomide • Oncophage (Heat Shock Protein Peptide Complex-96)
14d
P2, N=590, Recruiting, Merck Sharp & Dohme Corp. | Trial completion date: Sep 2024 --> Dec 2023 | Trial primary completion date: Sep 2024 --> Dec 2023
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor)
|
Keytruda (pembrolizumab) • lenvatinib
15d
MiR-126-5p restoration impaired TMZ resistance of GBM cells. In conclusion, our results provided a novel insight into acquired TMZ resistance of GBM cells and suggested LINC00511 as a potential biomarker or therapeutic target for GBM patients.
Journal
|
MIR126 (MicroRNA 126)
|
temozolomide
15d
Clinical • New P4 trial
|
PIAS4 (Protein Inhibitor Of Activated STAT 4)
|
temozolomide
15d
Additionally, several phase I/II clinical trials are underway using vaccines, oncolytic viruses, antibodies, and chimeric antigen receptor T cells targeting glioma cells. Co-opting the immune system as a therapeutic partner against GBM is in early stages of investigation, and the potential use of such approaches as treatment adjuncts is indispensable for combating this highly heterogeneous disease.
Journal
|
CSF1R (Colony stimulating factor 1 receptor)
15d
Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase) • GLS2 (Glutaminase 2)
|
MGMT promoter methylation
15d
Herein, transcriptomic analysis of 177 well-defined DDR genes was performed with normal and GBM specimens (n = 137) from The Cancer Genome Atlas and further integrated with the expression profiling of histone deacetylase 6 (HDAC6) inhibition in temozolomide (TMZ)-resistant GBM cells and patient-derived tumor cells...Our findings uncover a regulatory network among HDAC6, Sp1, and DDR genes for drug resistance and survival of GBM cells. Furthermore, MPT0B291 may serve as a potential lead compound for GBM therapy.
Journal • Epigenetic controller
|
HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1)
|
temozolomide
15d
Our findings uncover the fundamental mechanisms underlying the interplay of m A RNA modification and histone modification in TMZ resistance and emphasize the therapeutic potential of targeting the SOX4/EZH2/METTL3 axis in the treatment of TMZ-resistant GBM.
Journal • Epigenetic controller
|
METTL3 (Methyltransferase Like 3) • SOX4 (SRY-Box Transcription Factor 4)
|
temozolomide
15d
Besides, they displayed a normal karyotype and had the potential to differentiate spontaneously three germ layers in vitro. Our model might be useful in studying the pathogenesis of gliocytoma patients.
Clinical • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • KLF4 (Kruppel-like factor 4) • SOX2
15d
P1/2, N=198, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting
Clinical • Enrollment closed • Combination therapy
|
CD163 (CD163 Molecule)
|
spartalizumab (PDR001) • BLZ-945
15d
P2, N=20, Recruiting, photonamic GmbH & Co. KG | Not yet recruiting --> Recruiting | Trial completion date: Nov 2026 --> Mar 2027 | Trial primary completion date: Nov 2022 --> Mar 2023
Clinical • Enrollment open • Trial completion date • Trial primary completion date
|
MGMT (6-O-methylguanine-DNA methyltransferase) • CD4 (CD4 Molecule)
|
MGMT promoter methylation
16d
In this study, three datasets (GSE23806, COSMIC, and TCGA) were used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance, and prognosis...In summary, AEBP1 was related with GSC-induced TMZ resistance. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase) • AEBP1 (AE Binding Protein 1)
|
AEBP1 overexpression
|
temozolomide
16d
We also identified several CD163-associated kinase, miRNA, and transcription factor targets in GBM, including LCK, miR-483, and ELF1. In conclusion, our study suggested CD163 as a prognostic biomarker and associated it with immune infiltration in GBM.
Journal
|
CD163 (CD163 Molecule) • MIR483 (MicroRNA 483)
|
CD163 expression
16d
BGM and BGD have been found to be antimicrobial effects. Boron compounds, especially the BGM, can provide a new therapeutic approach for the treatment of glioblastoma with their anticancer, antioxidant, and antimicrobial effects.
Preclinical • Journal
|
CAT (Catalase)
16d
Novel natural molecules and phyto-extracts have been proposed as adjuvants to sensitise the response to Temozolomide (TMZ)...Furthermore, as main key regulators of type II programmed cell death, p53, p21 and CDK4 were also investigated and were inhibited by GS treatment. In conclusion, GS extract could be considered as an autophagy inducer in glioblastoma cells U87Mg.
Journal
|
CDK4 (Cyclin-dependent kinase 4) • CASP9 (Caspase 9) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
temozolomide
16d
XChIp showed that FKBP51s binds CCND1 gene in a closed-chromatin configuration. Our finding suggests that the dynamism of PD-L1 expression in GBM follows cyclin-D fluctuation and raises the hypothesis that FKBP51s might participate in the events that govern cyclin-D oscillation.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CCND1 (Cyclin D1) • FKBP5 (FKBP Prolyl Isomerase 5)
|
PD-L1 expression • CCND1 expression
16d
GBM-N019 also synergized with and enhanced the anti-GBM activities of palbociclib in vitro and in vivo. In conclusion, our results suggested that GBM-N019 possesses good translational relevance as a potential anti-glioblastoma drug candidate worthy of consideration for clinical trials against recurrent glioblastomas.
Preclinical • Journal
|
STAT3 (Signal Transducer And Activator Of Transcription 3) • CDK6 (Cyclin-dependent kinase 6)
|
Ibrance (palbociclib)
16d
We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.
Journal
|
MMP2 (Matrix metallopeptidase 2) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • MMP9 (Matrix metallopeptidase 9)
16d
Furthermore, intraperitoneal administration of 150 mg/kg NSC139021 significantly suppressed the growth of human and mouse glioblastoma in vivo. Our study suggests that NSC139021 may be a potential chemotherapy drug for the treatment of glioblastoma by targeting the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway.
Journal
|
CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • SKP2 (S-phase kinase-associated protein 2)
16d
Parallel demographic, clinical, and histologic pattern analyses were merged with the molecular subgrouping to yield the first inclusive multi-platform classification for IDH-wild-type glioblastoma. This straightforward classification with diagnostic and prognostic significance may be readily used in neuro-oncological practice and lays the foundation for personalized targeted therapy approaches.
Journal
|
EGFR (Epidermal growth factor receptor) • FGFR3 (Fibroblast growth factor receptor 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1)
16d
This review article aims to provide a general overview of the current state of glioblastoma immunotherapy. Information was compiled through a literature search conducted on PubMed and clinical trials between 1961 to 2021.
Review • Journal • Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden)
|
TMB-L
16d
Our findings highlight how LOS, in addition, antagonizes the previously documented neoangiogenetic, profibrotic, and immunosuppressive effects of Ang II and drastically inhibits its stimulatory effects on local estrogen production, sustaining glioblastoma cell growth. Thus, Losartan may represent an adjuvant pharmacological tool to be repurposed prospectively for glioblastoma treatment.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor)
|
PD-L1 expression
|
losartan potassium
16d
Overall, our results are close to the ones reported in the previous phase 2 study, despite the fact that we had a longer survival. We showed the encouraging activity and tolerability of this treatment in recurrent glioblastoma patients when used as a second-line treatment.
Clinical • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
Stivarga (regorafenib)
16d
Microglia were also extensively accumulated in the tumor formed in LPS-primed TNFR2 mice. Accordingly, our findings demonstrate that aggravation of microglia activation by peripheral inflammatory challenge and a loss of TNFR2 function might lead to the promotion of glioma growth.
Preclinical • Journal
|
TNFA (Tumor Necrosis Factor-Alpha) • ITGAM (Integrin, alpha M) • TNFRSF1B (Tumor necrosis factor receptor superfamily member 1B)
16d
In particular, a combination comprising the MRP1 inhibitor reversan, PF-2545920 and MY-5445, all at low micromolar concentrations, afforded nearly complete inhibition of glioblastoma cell growth. Thus, the potent suppression of glioblastoma cell viability may be achieved by combining MRP1 inhibitors with PDE inhibitors at a lower toxicity than that of the standard chemotherapeutic agents, thereby providing a new combination therapy for this challenging malignancy.
Journal
|
ABCC1 (ATP Binding Cassette Subfamily C Member 1)
|
PF-02545920
16d
Therefore, this approach may yield a general strategy to fight cancer. Our mechanistic studies have so far implicated induction of STAT-1 in this M2→M1 switch, but further studies are needed to understand the involvement of other factors such as the lipid metabolites resolvins in the CC-evoked anticancer pathways.
Journal
|
STAT1 (Signal Transducer And Activator Of Transcription 1)
16d
Furthermore, it is also associated with tumor mutation burden and microsatellite instability in various tumors. PLOD3 acts as an inducer of various cancers, and it could be a potential biomarker for prognosis and targeted treatment.
Journal • Tumor Mutational Burden • Pan tumor
|
TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8)
16d
PD-1 blocking antibodies did not have an additive effect with GiNKs for prolonging survival. GiNKs may represent a promising cell-based immunotherapy for patients with GBM and are minimally affected by the PD-1/PD-L1 immune evasion axis in GBM.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • IL2 (Interleukin 2)
|
PD-L1 expression • PD-1 expression
16d
Based on the information available, C3G could represent a new biomarker for GBM diagnosis, prognosis, and personalised treatment of patients in combination with other GBM molecular markers. The quantification of C3G levels in circulating tumour cells (CTCs) in the cerebrospinal liquid and/or circulating fluids might be a useful tool to improve GBM patient treatment and survival.
Review • Journal
|
FGFR1 (Fibroblast growth factor receptor 1)
16d
Samples taken from the combined treatment group demonstrated an increased Desmin/CD31 and col IV/vessel ratio, suggesting an increased rate of vascular normalization. Our results demonstrate that BTK-mTOR inhibition disrupts the population of GBM-CSCs and contributes to normalizing GBM vascularization and thus, may serve as a basis for developing therapeutic strategies for chemoresistant/radioresistant GBM.
Journal
|
CD31 (Platelet and endothelial cell adhesion molecule 1)
|
Calquence (acalabrutinib) • sirolimus
16d
In multivariate analysis, a high integrin α5 protein expression level was confirmed as an independent prognostic factor in the subpopulation of patients who completed the temozolomide-based first-line treatment for predicting OS over age, extent of surgery, RPA score and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (p = 0.029). In summary, for the first time, our study validates that a high integrin α5 protein expression level is associated with poor prognosis in GBM and confirms its potential as a therapeutic target implicated in the Stupp protocol resistance.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide
16d
Besides the effects of PFI-3 on GBM cells in vitro, we found that PFI-3 markedly potentiated the anticancer effect of TMZ in an intracranial GBM animal model, resulting in a marked increase in survival of animals bearing GBM tumors. Taken together, we identified the BRG1 and BRM subunits of SWI/SNF as novel targets in GBM and revealed the therapeutic potential of applying small molecule inhibitors of SWI/SNF to improve the clinical outcome in GBM using standard-of-care chemotherapy.
Journal
|
SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
|
temozolomide
16d
Results showed that luteolin induces apoptosis and autophagy and that the luteolin-induced autophagy promotes cell survival. Therefore, an appropriate combination therapy involving luteolin and an autophagy inhibitor is expected to improve the prognosis of GBM treatment.
Preclinical • Journal
|
CASP3 (Caspase 3)
16d
When administered as late treatment to a well-established glioblastomas, R-613 appeared to be less effective. Notably the uninfected tumor cells derived from the explanted tumor masses were still susceptible to R-613 infection ex vivo, thus suggesting that multiple treatments could enhance R-613 therapeutic efficacy, making R-613 a promising oncolytic HSV candidate for glioblastoma treatment.
Clinical • Journal • IO biomarker
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFRvIII expression
16d
Senescent astrocytes secreted HGF to activate Met in glioma cells and promote their migration and invasion in vitro, which could be blocked by HGF-neutralizing antibodies or the Met inhibitor crizotinib. Treatment with the senolytic drug ABT-263 (navitoclax) selectively killed senescent astrocytes in vivo, significantly attenuating growth of glioma cells implanted in pre-irradiated brains. These results indicate that SASP factors in the irradiated tumor microenvironment drive GBM growth via RTK activation, underscoring the potential utility of adjuvant senolytic therapy for preventing GBM recurrence after radiotherapy.
Journal
|
CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
Xalkori (crizotinib) • navitoclax (ABT 263)
17d
Clinical • Enrollment open
|
FUS (FUS RNA Binding Protein)
17d
We also confirmed that knockdown of HSPA7 might increase the efficiency of anti-PD1 therapy utilizing the GBO model, highlighting its potential as a novel target for immunotherapy. Our results indicated that HSPA7 could be a novel immunotherapy target for GBM patients.
Observational data • Journal • PD(L)-1 Biomarker • IO biomarker
|
SPP1 (Secreted Phosphoprotein 1) • YAP1 (Yes associated protein 1)
17d
We also discuss novel therapeutic targets that can aid in resolving reticular connections between TAM/Ms and CD8+ T cells, including depletion and reprogramming TAM/Ms and novel TAM/Ms-CD8+ T cell cofactors with potential translational usage. In addition, we highlight the challenges and discuss future perspectives of this crosstalk between TAM/Ms and CD8+ T cells.
Journal
|
CD8 (cluster of differentiation 8)
|
CD8 positive
17d
BRCAness status identified by accurate biomarkers can ultimately predict responsiveness to PARPi therapy, thereby allowing patient selection for personalized treatment. This review discusses potential biomarkers of BRCAness for a 'precision medicine' of GBM patients.
Review • Journal • BRCA Biomarker • PARP Biomarker
|
EGFR (Epidermal growth factor receptor) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • BRCA (Breast cancer early onset)
|
BRCA1 mutation • BRCA mutation
17d
In this prospective cohort, we found no significant associations between the inflammatory biomarkers CRP and WBC and the development of glioma. NLR and IGF-1 were associated with risk in women, but not men. When considered with previous studies, further investigation of NLR and IGF-1 as markers of glioma risk appears warranted, particularly in women.
Clinical • Journal
|
IGF1 (Insulin-like growth factor 1) • CRP (C-reactive protein)
17d
Our study proved the accuracy and efficiency of random forest classifier for GBM subtyping, which could provide a convenient and efficient method for subtyping Proneural and Mesenchymal GBM.
Journal
|
CD276 (CD276 Molecule)
17d
Moreover, the IFNGrGS score had solid prognostic value and the potential to screen ICB and radiotherapy sensitive populations. Collectively, our study provided insights into the role of IFNG on the GBM immune microenvironment and offered feasible information for optimizing the treatment of GBM.
Clinical • Journal • Gene Signature • IO biomarker
|
EGFR (Epidermal growth factor receptor) • IFNG (Interferon, gamma) • TGFB1 (Transforming Growth Factor Beta 1) • IL10 (Interleukin 10) • TGFBI (Transforming Growth Factor Beta Induced) • IL4 (Interleukin 4)
|
EGFR mutation • IFNG-L
17d
They also exhibited superior antitumor activity in vivo when compared to 2173 CAR T cells. The broad specificity of 806 CAR T cells to EGFR alterations gives us the potential to target multiple clones within a tumor and reduce opportunities for tumor escape via antigen loss.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR amplification
17d
P1, N=15, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2024 --> Sep 2024 | Trial primary completion date: Feb 2022 --> Sep 2022
Trial completion date • Trial primary completion date • Combination therapy
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
spartalizumab (PDR001) • sabatolimab (MBG453)
19d
Clinical • Trial suspension
|
MGMT (6-O-methylguanine-DNA methyltransferase) • IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • CSF2 (Colony stimulating factor 2) • CD4 (CD4 Molecule) • LAMP1 (Lysosomal Associated Membrane Protein 1)
|
temozolomide • Leukine (sargramostim)
19d
P1, N=45, Recruiting, Pediatric Brain Tumor Consortium | Trial primary completion date: Sep 2021 --> Mar 2022
Trial primary completion date
|
TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)
|
sotigalimab (APX005M)
19d
Most importantly, treatment with DLPC inhibits glioblastoma tumor growth in vivo in heterotopic and orthotopic xenograft mouse models. These data indicate a tumor suppressor role of NR5A2 in the nervous system and render this nuclear receptor a potential pharmacological target for the treatment of nervous tissue-related tumors.
Journal
|
CDKN1B (Cyclin dependent kinase inhibitor 1B) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
19d
Our work identify functionally distinct TAM subpopulations in the growth of different glioma subtypes. Notably, we uncover a potential responsiveness of resistant mesenchymal-like gliomas to combined anti-angiogenic therapy and CSF1R inhibition. These data highlight the importance of characterization of the microenvironment landscape in order to optimally stratify patients for TAM-targeted therapy.
Journal
|
PDGFB (Platelet Derived Growth Factor Subunit B)
|
Turalio (pexidartinib)
19d
MTT assay showed significant concentration dependent cytotoxic activity and the IC value was calculated as 21μg/ml. Further, annexin V/FITC staining by FACS, the expression of caspase 3 and 7 and the circadian genes clock and Bmal1 using RT-PCR and the generation of intracellular ROS, cell cycle analysis by FACS revealed the ability of AEL to induce effective apoptosis.
Preclinical • Journal
|
CASP3 (Caspase 3) • ARNTL (Aryl Hydrocarbon Receptor Nuclear Translocator Like)
20d
(4) This study suggests that performance status and extent of resection are significant determinants of patient response to treatment. In the case of elderly patients with borderline performance status and GTR or those with good performance status and STR, also described as "mixed traits", it may be beneficial to pursue single modality treatment, ideally based on MGMT promoter methylation status as opposed to bimodality treatment in order to maintain the best QOL.
Clinical • Retrospective data • Review • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
temozolomide
20d
The discovery of TERT promoter mutations in numerous gliomas has opened the door for a better molecular classification of gliomas, and TERT status is associated with survival. Further studies will help in elucidating the value of TERT promoter mutations as biomarkers in clinical practice, and eventual therapeutic targets.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
IDH1 R132H • TERT promoter mutation • TERT mutation
20d
Journal • CAR T-Cell Therapy
|
BRD4 (Bromodomain Containing 4)
20d
Symptom duration was associated with an H3 K27M mutation in intramedullary astrocytoma. MRI features were heterogeneous, and no imaging feature was able to predict the H3 K27M mutation. The H3 K27M mutation did not impact survival outcome in spinal histologically high-grade astrocytoma.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation
21d
Furthermore, the CT2A model was completely resistant to virus therapy, while in the GL261N4 model rQNestin34.5v1 treatment resulted in enhanced macrophage recruitment, impaired tumor progression, and long-term survival of a few animals. We conclude that prolonged intratumoral viral presence correlates with immune cell recruitment, and both are needed to enhance anti-tumor immunity.
Clinical • Journal
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
CAN-3110
21d
Thus, circSERPINE2 promotes BCL2 expression through sponging miR-324-5p and miR-361-3p. In conclusion, our study revealed the biological function and mechanism of circSERPINE2 in glioblastoma progression and that circSERPINE2 could be a potential therapeutic target for glioblastoma.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • MIR324 (MicroRNA 324) • MIR361 (MicroRNA 361)
|
BCL2 expression
21d
P2, N=75, Recruiting, Wake Forest University Health Sciences | Trial completion date: Sep 2021 --> Sep 2022 | Trial primary completion date: Sep 2021 --> Sep 2022
Trial completion date • Trial primary completion date
|
APOE (Apolipoprotein E)
|
ramipril
22d
SON knockdown inhibits proliferation and clonogenicity of GBM cells in vitro and significantly suppresses tumor growth in orthotopic xenografts in vivo. Collectively, our study reveals that SON-mediated RNA splicing is a GBM vulnerability, implicating SON as a potential therapeutic target in brain tumors.
Journal
|
PTBP1 (Polypyrimidine Tract Binding Protein 1)
22d
The adverse impact of increasing brain tumor size on the efficacy of antibody-drug conjugates (ADCs) was investigated preclinically then validated with clinical data. Both preclinical and clinical data showed intra-tumoral concentration and efficacy of Depatux-m inversely correlated with tumor size. This finding merit further investigation with pretreatment tumor volume as a predictor for response to ADCs, in both gliomas and other solid tumors.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR amplification
|
depatuxizumab mafodotin (ABT-414) • depatuxizumab (ABT-806)
22d
NRG2 is highly expressed in gliomas of different grades and regulates GFAP expression in glioma cells at least partly via the Akt signaling pathway to affect the survival of glioma patients.
Journal
|
AKT1 (V-akt murine thymoma viral oncogene homolog 1) • GFAP (Glial Fibrillary Acidic Protein)
|
perifosine (D21266)
22d
Our results indicate that PAK3 plays a unique role among PAKs in glioma development and may represent a potential therapeutic target.
Journal
|
PAK2 (P21 (RAC1) Activated Kinase 2)
23d
In subsequent in vivo experiments, we found that CYT387 inhibited subcutaneous nude mouse tumor growth but had little impact on intracranial orthotopic xenografts, probably due to a limited ability to penetrate the blood-brain barrier (BBB). These results suggest that CYT387 has potential as a new antiglioblastoma drug, but an approach to allow passage through the blood-brain barrier (BBB) is needed.
Journal
|
YAP1 (Yes associated protein 1) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon)
|
momelotinib (CYT 387)
23d
The study demonstrates that an insertion variant of MGMT rs10659396 confers susceptibility to glioma by downregulating MGMT expression through disrupting a STAT1 binding site.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase) • STAT1 (Signal Transducer And Activator Of Transcription 1)
24d
P1, N=36, Completed, Ziopharm | Active, not recruiting --> Completed | Trial completion date: Jun 2021 --> Jan 2021
Trial completion • Trial completion date
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule)
|
Ad-RTS-hIL-12 • veledimex (INXN-1001)
24d
P1, N=28, Recruiting, Pediatric Brain Tumor Consortium | Active, not recruiting --> Recruiting
Enrollment open
|
CD4 (CD4 Molecule)
|
aderbasib (INCB7839)
24d
Clinical • New P2 trial
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • CD34 (CD34 molecule)
|
IDH2 mutation
|
temozolomide • carmustine • Neupogen (filgrastim)
24d
Indeed, experiments in which the mitochondrial apoptosis threshold was lowered by antagonizing Mcl-1 re-established sensitivity to IZI1551+marizomib in otherwise resistant cells. Overall, our study demonstrates a high efficacy of combination treatments with a latest-generation TRAIL receptor agonist and the BBB permeant proteasome inhibitor marizomib in relevant GBM cell models, as well as strategies to further enhance responsiveness and to sensitize subgroups of otherwise resistant GBM cases.
Journal
|
MCL1 (Myeloid cell leukemia 1) • CASP8 (Caspase 8)
|
marizomib (NPI-0052)
24d
In conclusion, stabilization of MULE upon KRIBB11 treatment is apparently an essential step for degradation of MCL-1 and the subsequent induction of apoptosis in A172 cells. Our results have expanded the knowledge on molecular pathways controlled by KRIBB11 and could be potentially effective for developing an inhibitory therapeutic strategy for glioblastoma.
Journal
|
MCL1 (Myeloid cell leukemia 1)
24d
Consequently, effective suppression of tumor growth and significantly improved medium survival time are observed when these miRNA nanomedicines were assessed in an orthotopic GBM xenograft model. This work indicated that our new polymeric nanoparticles successfully mediate inhibition of miR-21 and miR-124 supplementation to significantly reduce tumorigenesis, and may have strong potential in GBM therapy.
Journal
|
MIR21 (MicroRNA 21)
24d
Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.
Preclinical • Journal • PARP Biomarker
|
CASP3 (Caspase 3) • CASP9 (Caspase 9) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1) • CDC25C (Cell Division Cycle 25C) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
24d
Combining AURKA inhibitors with inhibitors of FAO extends overall survival in orthotopic GBM PDX models. Taken together, these data suggest that simultaneous targeting of oxidative metabolism and AURKAi might be a potential novel therapy against recalcitrant malignancies.
Journal
|
AURKA (Aurora kinase A) • PPARA (Peroxisome Proliferator Activated Receptor Alpha)
24d
The reduction of CD31-positive endothelial cells confirmed the anti-angiogenic effects of the nanoparticles. The results indicate that the intranasal delivery of the self-assembled nanoparticles of antagomir-21 and RAP is an efficient treatment of glioblastoma.
Journal
|
PTEN (Phosphatase and tensin homolog) • MIR21 (MicroRNA 21) • CD31 (Platelet and endothelial cell adhesion molecule 1)
24d
More importantly, I-1 showed higher safety than temozolomide and different mechanism from temozolomide in the C6 glioma orthotopic model. All the evidence demonstrated that N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents could be promising for the glioma management.
Journal
|
CDH1 (Cadherin 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • MMP9 (Matrix metallopeptidase 9)
|
temozolomide
24d
Irradiation leads to measurable MD reduction in white matter, progressing with both increasing dose and time. Treatment with protons reduces this effect most likely due to a lower total dose in the surrounding white matter. Further investigations are needed to assess whether those MD changes correlate with known radiation induced side-effects.
Journal
|
IL33 (Interleukin 33)
24d
Out of 28 patients, 15 (62.5%) patients died of disease. Conclusion Diffuse midline gliomas with H3K27M mutation is an aggressive entity with a broad morphological spectrum.
Journal
|
ATRX (ATRX Chromatin Remodeler)
24d
Increased CD133 protein expression is associated with sooner distant tumor recurrence on MRI in glioblastoma patients and patients with high-grade gliomas and improved TTL on MRI in glioblastoma patients. Based on the current evidence from 1086 patients with high-grade gliomas, CD133 overexpression is a valuable marker to predict tumor relapse and tumor recurrence patterns in patients with high-grade gliomas.
Retrospective data • Review
|
CD133
|
CD133 expression • CD133 overexpression
24d
In conclusion, our study revealed that the high expression of CD74 was associated with poor prognosis and high immune infiltration. CD74 could be used as a potential target for glioma treatment and as a biomarker to predict the prognosis of glioma patients.
Journal
|
CD74 (CD74 Molecule)
|
CD74 expression
24d
Most of the HDAC family significantly correlated with the glioma grade, IDH1 mutation, and 1p/19q codeletion. HDAC1 was both a prognostic and immune infiltration indicator and a central component of the HDAC1-related signature for precise prognosis prediction in glioma.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • HDAC1 (Histone Deacetylase 1) • HDAC11 (Histone Deacetylase 11) • CD4 (CD4 Molecule)
|
IDH1 mutation
24d
The level of RNA-mediated gene silencing achieved in Parental versus Stable GFP U87 and MDA-MB-231 cells agreed with the observed levels of polyplex/lysosome colocalization, supporting the established concept that endosomal escape is the rate-limiting step for RNA interference. These findings indicate that lysosomal labels can profoundly alter cellular function and cell-nanocarrier interactions, presenting critical new considerations for researchers investigating nanoparticle trafficking.
Journal
|
LAMP1 (Lysosomal Associated Membrane Protein 1)
24d
TGF-β and its downstream mediator TSP1 are important mediators of the MT network in GBM and blocking this pathway could potentially help to break the complex MT driven invasion/ resistance network.
Journal
|
THBS1 (Thrombospondin 1) • TGFB1 (Transforming Growth Factor Beta 1)
24d
Increased sensitivity to temozolomide was observed upon loss of BRG1-ATPase catalytic domain. These findings highlight the role of ATPase domain of BRG1 in regulating redox homeostasis and sensitivity to oxidative stressors in glioma cells. BRG1 mutation created vulnerability to elevated ROS levels can be therapeutically exploited, with ROS stressors as a promising therapeutic target for the treatment of BRG1-mutant cancers.
Journal
|
SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
|
SMARCA4 mutation
|
temozolomide
24d
Background: Since late 2018, 2 TRK inhibitors—larotrectinib and entrectinib—have been approved by the EMA and FDA for treating patients with advanced solid tumors harboring an NTRK fusion and progressive disease or no therapeutic alternatives. The rate of broad testing for NTRK fusions across patients with solid tumors remains low, and many HCPs lack awareness of when to consider a TRK inhibitor. Educational activities designed to address these deficiencies would be of clear benefit to HCPs treating patients with advanced solid tumors. A detailed analysis of HCP trends will be presented.
Clinical
|
MSI (Microsatellite instability) • NTRK (Neurotrophic receptor tyrosine kinase)
|
MSI-H/dMMR • NTRK fusion
|
Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
24d
P1, N=71, Active, not recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Recruiting --> Active, not recruiting | Trial completion date: Aug 2020 --> Jan 2022 | Trial primary completion date: Aug 2020 --> Jan 2022
Clinical • Enrollment closed • Trial completion date • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MCL1 (Myeloid cell leukemia 1) • CDK9 (Cyclin Dependent Kinase 9)
|
IDH1 R132H
|
temozolomide • zotiraciclib (TG02)
25d
In vitro, the UPR-inducer 2-Deoxyglucose (2DG), which blocks glycosylation in the endoplasmic reticulum, was enhanced up to 3-fold by inhibition of protein synthesis...Analyzing whether UPR induction vice versa also enhanced protein synthesis inhibition, we found that activity of the immunotoxin Moxetumomab was increased by 2 to 17-fold in combination with UPR-inducers 2DG or Tunicamycin (TM)... Combining UPR and inhibition of protein synthesis achieves strong synergistic cell death in several malignancies. Because immunotoxins induce target specific inhibition of protein synthesis, the combination with UPR opens a novel, so far undescribed therapeutic window which may warrant clinical evaluation.
ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
|
Lumoxiti (moxetumomab pasudotox) • deoxyglucose
25d
P2, N=0, Withdrawn, University of Aarhus | N=20 --> 0 | Suspended --> Withdrawn
Enrollment change • Trial withdrawal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide
26d
The importance of Sox21 in the progression of malignant melanoma could be due to the interaction with other SOX genes such as Sox10, which is increased in melanoma, or Sox2, whose complex formation with Sox21 in glioblastoma has been described. Our data indicate that Sox21 also plays an important role as a tumor suppressor in melanoma and could therefore represent an important starting point for future therapies.
SOX10 (SRY-Box 10) • SOX2 • MITF (Melanocyte Inducing Transcription Factor)
26d
Also, PPI result showed SGO2 to be a potential hub protein, which was related to the expression of AURKB and FOXM1. SGO2 expression positively correlates with WHO pathological grading and patient survival, suggesting that SGO2 is a biomarker that is predictive of disease progression in patients with gliomas.
Clinical • Journal
|
AURKB (Aurora Kinase B) • FOXM1 (Forkhead Box M1)
27d
Quantification by qRT-PCR showed increased expression levels of long non-coding RNAs RP11-838N2.4 and XIST in glioma cells treated with either bee venom or melittin. Overall, this study provides preliminary insight on molecular mechanisms via which bee venom and its main components can impact viability of glioma cells and warrants further investigation of its anticancer potential in gliomas.
Journal
|
BAX (BCL2-associated X protein) • BAK1 (BCL2 Antagonist/Killer 1) • XIST (X Inactive Specific Transcript)
|
BAX expression
|
Apitox (honeybee venom)
27d
Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase) • LANCL2 (LanC Like 2)
|
EGFR amplification • EGFR expression • EGFR overexpression • MGMT promoter methylation
27d
The inflammatory phenotype of changes was associated with poor survival. A significant inflammatory response was found in patients with GBM and correlated with clinical features, the molecular profile of the tumour and poor survival.
Clinical • Retrospective data • Journal
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
TP53 overexpression
27d
RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.
Journal
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • TERT (Telomerase Reverse Transcriptase)
|
KRAS mutation • BRAF mutation • NRAS mutation • IDH1 mutation • KRAS exon 3 mutation
27d
Studies with conflicting results are discussed and future possibilities are put forward. A collective understanding of the studies on these steroid hormones in glioma may serve to create an amalgamated therapeutic approach; and thereby, augment the efforts in tackling this deadly disease.
Review • Journal
|
ER (Estrogen receptor) • AR (Androgen receptor)
27d
In addition, the signature may also improve the prognostic power of age. In summary, our results suggested that the lymphocyte activation-associated gene signature is a promising factor for the survival of patients, which is helpful for the prognosis of GBM patients.
Journal • Gene Signature
|
TCF3 (Transcription Factor 3) • IGFBP2 (Insulin-like growth factor binding protein 2)
27d
FEZF1-AS1 had oncogenic function in the advancement of GBM by targeting miR-363-3p/NOB1, which made FEZF1-AS1 a potential biomarker for GBM treatment.
Journal
|
MIR363 (MicroRNA 363)
27d
Finally, TSSC4 suppresses tumorsphere formation and tumor growth by inhibiting autophagy and maintaining cell survival in tumorspheres. Taken together, sustainable cancer cell growth can be achieved by autophagy inhibition via TSSC4 expression.ABBREVIATIONS: 3-MA: 3-methyladenine; ACTB: actin beta; CQ: chloroquine; EGFRvIII: epidermal growth factor receptor variant III; ERBB2: erb-b2 receptor tyrosine kinase 2; GBM: glioblastoma multiforme; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule Associated protein 1 light chain 3; TSSC4: tumor suppressing subtransferable candidate 4.
Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TYK2 (Tyrosine Kinase 2)
|
EGFR mutation • EGFRvIII mutation • EGFRvIII expression
|
chloroquine phosphate
27d
In addition, high PARP1 expression was positively associated with microsatellite instability event in COAD, KIRP, BRCA, glioblastoma multiforme (GBM), lung squamous cell carcinoma (LUSC), LGG, READ, UCEC, SKCM and LUAD (P < 0.05). Our results highlight the significance of PARP1 alterations as pan-cancer predictive biomarkers for ICI treatment, and its expression levels seem to be correlated with the status of immunotherapy-associated signatures, thus may be a promising biomarker for predicting ICI response in several tumors.
Journal • Tumor Mutational Burden • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker • Pan tumor
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • BRCA (Breast cancer early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CD4 (CD4 Molecule)
|
PD-L1 expression • TMB-H • LAG3 expression • CTLA4 expression • PARP1 overexpression
27d
TP53 was the most commonly dysregulated gene followed by PTEN and EGFR. TTN and PTEN (lowest survival at 12 months) and TTN and MDM4 (lowest survival at 24 months) mutations were associated with the worst prognosis. These new insights may provide the foundation for developing new future therapies for these patients.
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • MDM4 (The mouse double minute 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • MUC16 (Mucin 16, Cell Surface Associated)
|
TP53 mutation • PTEN mutation
27d
After the US Food and Drug Administration approval of Larotrectinib, the detection of NTRK fusion in many late-stage cancers have become a standard part of management... We expand the list of tumors that may be positive for NTRK fusion protein by IHC. The high diagnostic sensitivity, cost-effectiveness, and rapid turnaround time, the monoclonal antibody (EPR17341) may potentially be used as a screening marker to rule in NTRK positive tumors especially when DNA or RNA-based molecular testing is not available.
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK3 fusion • ETV6-NTRK3 fusion • NTRK fusion • NTRK positive
|
VENTANA pan-TRK (EPR17341) Assay
|
Vitrakvi (larotrectinib)
27d
He received postoperative hypofractionated radiotherapy with concurrent temozolomide. Unfortunately, within 2 months of surgery the patient died. In summary, glioblastoma with rhabdoid feature is a rare and very aggressive astrocytic tumor which may not show INI-1 loss as in our presented case.
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • GFAP (Glial Fibrillary Acidic Protein) • SYP (Synaptophysin)
|
temozolomide
28d
P2, N=45, Recruiting, OHSU Knight Cancer Institute | Trial completion date: May 2023 --> May 2024 | Trial primary completion date: May 2021 --> Aug 2023
Clinical • Trial completion date • Trial primary completion date
|
PD-L1 (Programmed death ligand 1)
|
Keytruda (pembrolizumab) • Feraheme (ferumoxytol injection)
29d
In summary, our findings point out that NDR1 functions as a tumor suppressor in GBM. NDR1 is identified as a novel regulator of YAP, which gives us an in-depth comprehension of the Hippo signaling pathway.
Journal
|
NDRG1 (N-Myc Downstream Regulated 1)
|
NDRG1 overexpression
29d
Implications: PRMT5 positively regulates the expression of FA genes. Inhibition of PRMT5 attenuates FA-dependent DNA repair pathway and sensitizes tumor cells to ICL agents.
Journal
|
MTAP (Methylthioadenosine Phosphorylase) • FANCA (FA Complementation Group A) • PRMT5 (Protein Arginine Methyltransferase 5)
29d
In rats bearing intracranial gliomas, regadenoson treatment results in increase of intratumoral temozolomide (TMZ) concentrations, yet no increased survival noted with combined TMZ therapy. The use of vasoactive mediators, like regadenoson, which transiently influences paracellular transport, should further be explored to evaluate their potential to enhance CNS treatment delivery to aggressive brain tumors. Implications: This study provides insight on the use of a vasoactive agent to increase exposure of the blood-tumor barrier to chemotherapy with intention to improve glioma treatment efficacy.
Preclinical • Journal
|
ADORA2A (Adenosine A2a Receptor)
|
temozolomide • Lexiscan (regadenoson)
29d
In conclusion, FGFR1-4 alterations are prevalent in solid tumors of diverse types, with the majority being gene amplifications and mutations. FGFR1-4 fusions only occur in a minority of cancer cases, and those with glioblastoma harboring FGFR3-TACC3 fusions may benefit from anlotinib.
Clinical • Journal • Next-generation sequencing
|
TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • LRP1B (LDL Receptor Related Protein 1B) • FGFR4 (Fibroblast growth factor receptor 4) • MUC16 (Mucin 16, Cell Surface Associated) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3)
|
FGFR1 amplification • FGFR2 mutation • FGFR3-TACC3 fusion • FGFR1 mutation • FGFR3 fusion • FGFR1 fusion
|
Focus V (anlotinib)
29d
These results strongly suggest that Torin2, compared to Torin1 or XL388, is more effective in suppressing mTORC1 and mTORC2, and therefore in the inhibition of the GB cell proliferation, dissemination and in overcoming resistance to therapy. These findings underscore the significance of Torin2 in the treatment of GB.
Journal
|
PTEN (Phosphatase and tensin homolog) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • AKT1S1 (AKT1 Substrate 1)
|
Torin1 • XL388
29d
Notably, TGF-β1/TβRI depletion dramatically reduces HGG-AM density and suppresses tumor growth. Altogether, our studies identify a specific microglia subpopulation and establish the cellular basis of interactions between HGG-AM and glioblastoma cells.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TGFB1 (Transforming Growth Factor Beta 1) • APOE (Apolipoprotein E)
|
SETD2 mutation
29d
P2, N=36, Recruiting, PharmAbcine | Trial completion date: Dec 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation
|
Avastin (bevacizumab) • olinvacimab (TTAC-0001)
30d
In contrast to other cancers, pan-TRK IHC appears of limited interest in this field because there is no 'on/off' IHC positivity criterion to distinguish between NTRK-rearranged and non-NTRK-rearranged gliomas. RNA sequencing analyses are necessary in FISH positive cases with less than 30% positive nuclei, to avoid false positivity when scoring is close to the detection threshold.
Journal
|
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • LMNA (Lamin A/C) • NACC2 (NACC Family Member 2) • NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK1 fusion • NTRK2 fusion • NACC2-NTRK2 fusion • NTRK fusion
|
VENTANA pan-TRK (EPR17341) Assay
1m
In addition, the administration of the proteasome inhibitor MG132 showed that fenofibrate promoted HIF-1α protein degradation in GBM. Hence, our results indicate that fenofibrate is a useful anti-GBM agent that modulates hypoxia-induced HIF-1α expression through multiple cellular pathways.
Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • CA9 (Carbonic anhydrase 9) • PPARA (Peroxisome Proliferator Activated Receptor Alpha)
|
HIF1A expression • CA9 expression
|
MG132 • fenofibrate
1m
Further analysis of marker expression in proliferating glioma cells and correlation with clinical outcome and susceptibility to irradiation and chemotherapy might help establish new biomarkers and therapies for glioma.
Journal
|
CD133 • CD44 • MKI67 (Marker of proliferation Ki-67) • NES (Nestin) • GFAP (Glial Fibrillary Acidic Protein)
1m
The GAPVAC-101 trial reported 50% APVAC1-induced and 84.7% APVAC2-induced immunogenicity with CD8+ and CD4+ T cell responses in 92% (12/13) and 80% (8/10) immune responders, respectively...Dexamethasone use had limited immunogenicity in a trial by Keskin et al (6/8)...Actively personalized vaccines aimed at unmutated peptides and neoantigens for patients with GBM are safe and highly immunogenic, particularly when administered in combination. Larger studies are warranted to investigate the role.
Clinical • Review • Journal
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
dexamethasone • APVAC1 vaccine
1m
Expectedly, targeted overexpression miR-139 or PDE2A in glioma with OCP system significantly repressed the stemness and decelerated glioma progression. Our findings elaborate on the inhibitory functions of PDE2A and miR-139 on GSC stemness and tumorigenesis, which may provide new prognostic markers and therapeutic targets for GBMs.
Journal
|
NOTCH1 (Notch 1) • HES1 • MIR139 (MicroRNA 139)
|
NOTCH1 expression
1m
It plays a vital role in the proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transformation of various tumor cells. This review summarizes the current body of knowledge on the biological functions and related molecular mechanisms of lncRNA HIF1A-AS2 in the development/progression of human tumors and other diseases.
Review • Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
HIF1A expression
1m
In conclusion, LIGHT was upregulated in more malignant gliomas including glioblastoma, IDH wildtype, and mesenchymal subtype. LIGHT was mainly involved in the immune function of macrophages, T cells, and APCs and served as an independent prognosticator in glioma.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
CD276 (CD276 Molecule)
1m
Mechanistically, ASIC1a negatively modulated glioma stemness via inhibition of the Notch signaling pathway and GSC markers CD133 and aldehyde dehydrogenase 1. ASIC1a is a tumor suppressor in gliomagenesis and stemness and may serve as a promising prognostic biomarker and target for GBM patients.
Journal
|
CD133
1m
In vivo results demonstrated a significant tumor-suppressing effect of 4-IPP when combined with radiation therapy. Collectively, our results showed that the targeted inhibition of MIF and DDT has the potential to strengthen current clinical strategies by enhancing the anticancer effects of radiation therapy.
Journal
|
SOX2 • MIF (Macrophage Migration Inhibitory Factor) • DCT (Dopachrome Tautomerase)
1m
The enhancement of PD-L1 in GBM was antagonized by paliperidone and risperidone as well as DRD2 selective inhibitor L741426...The present study suggests that DRD2 may be involved in regulating the PD-L1 expression in GBM and the microenvironment of GBM. Our results provide a valuable therapeutic strategy and indicate that treatments combining DRD2 antagonist paliperidone with standard immunotherapy may be beneficial for GBM treatment.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • MRC1 (Mannose Receptor C-Type 1) • DRD2 (Dopamine Receptor D2)
|
PD-L1 expression • CD20 expression • MRC1 expression • DRD2 expression
|
risperidone
1m
There was no difference in median Ki-67 LI between IDH-mutated and IDH-wildtype glioblastomas (p = 0.9) and Ki-67 LI was not associated with survival in glioblastomas in neither univariate (p = 0.9) nor multivariate analysis including MGMT promoter methylation status and excluding IDH-mutated glioblastomas (p = 0.2). Ki-67 may be of value in the differential diagnostic setting, but it must not be over-interpreted in the clinico-pathological context.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
1m
This may play a role in disease classification and inclusion criteria for clinical trials. Gliosarcoma mutations with potential therapeutic indications include BRAF, EGFR, CDKN2A, NF1, and PTEN.
Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NF1 (Neurofibromin 1)
|
BRAF mutation • PTEN mutation
1m
Molecular testing to fulfill the revised WHO criteria is, however, not always available worldwide, and in that case, an integrated diagnosis combining all available complementary information is highly recommended. This review discusses controversial issues surrounding legacy grading systems and newly identified potential genetic markers of adult diffuse gliomas and provides perspectives on future grading systems.
Clinical • Review • Journal
|
EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
|
EGFR mutation • EGFR amplification • CDKN2A deletion • TERT promoter mutation • TERT mutation
1m
Treatment with OAT-1746 modified the TME resulting in reduced glioma growth and increased antitumor effects of the anti-PD-1 antibody. Our findings provide the evidence that inhibition of ARG1/2 activity in tumor cells and myeloid cells in the TME unblocks antitumor responses in myeloid cells and NK cells, and improves the efficacy of the PD-1 inhibition.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
ARG2 (Arginase 2) • ITGAM (Integrin, alpha M)
|
OATD-02
1m
U87, LN229 and C6 cells were also cultured in multi-well chambers to obtain proteins for Western blotting. We used primary antibodies against 3β-hydroxysteroid dehydrogenase (3β-HSD), 17α-hydroxilase/17,20-lyase (P450c17), 17β-hydroxysteroid dehydrogenase (17β-HSD) and 5α-reductase. Immunocytochemistry, and immunofluorescence results revealed that glioblastoma cells express 3β-HSD, P450c17, 17β-HSD and 5α-reductase proteins in their cytoplasm. Moreover, Western blot analyses revealed bands corresponding to the molecular weight of these four enzymes in the three GB cell lines. Thus, glioblastoma cells have the key enzymatic machinery necessary to synthesize androgens, and these enzymes might be useful targets for new therapeutic approaches.
Journal
|
AR (Androgen receptor) • CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1)
|
AR expression
1m
IDH mutation and MGMT promoter methylation status in GBMs can be assessed effectively by IVIM and DSC. Besides, D* was the independent predictor of IDH mutation status.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT unmethylation • MGMT promoter methylation
1m
Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity...This PTV-loaded nanocarrier triggers apoptosis by reducing the mRNA level of anti-apoptotic genes NF-kβ, IL-6, BIRC1 and BIRC5 by 89%, 33%, 81% and 63%, respectively, and the cell viability by >60%. Overall, our results suggest the potential of these hybrid nanocarriers for the targeted therapy of GBM and other tumors overexpressing integrin receptors.
Clinical • Journal
|
IL6 (Interleukin 6) • BIRC5 (Baculoviral IAP repeat containing 5)
|
Livalo (pitavastatin)
1m
We also observed significant positive correlations between monocyte proportion and expression of PD-L1 and PD-L2 (R = 0.54 and 0.68, respectively). Overall, the findings highlight specific roles of the TME in biology and classification of CNS tumors, where specific immune cell admixtures correlate with tumor types and genomic alterations.
Journal • PD(L)-1 Biomarker • IO biomarker • Epigenetic controller
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PD-L2 (Programmed Cell Death 1 Ligand 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
|
PD-L1 expression • EGFR amplification • CDKN2A deletion
1m
Our data suggest that the combination therapy may inhibits cell proliferation, increases apoptosis, and increases the autophagy on LN229 and LN18. The potential molecular mechanisms were related to mitochondrial metabolism and respiratory chain inhibition.
Journal
|
PTGS2 (Prostaglandin-Endoperoxide Synthase 2)
|
temozolomide • celecoxib oral
1m
In the present study, we show that rods show immunoreactivity for the nucleotide synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase. By analogy with the IMPDH filaments that have been described previously, we postulate that rods regulate the activity of nucleotide-synthesizing enzymes in the nucleus by sequestration, with important implications for glioma behavior.
Journal
|
TUBB3 (Tubulin beta 3 class III)
1m
While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • STAT3 (Signal Transducer And Activator Of Transcription 3)
|
EGFR mutation • MET amplification • EGFR amplification • EGFRvIII mutation
|
Avastin (bevacizumab) • Tagrisso (osimertinib) • temozolomide
1m
Temozolomide (TMZ) is the recommended drug for the standard treatment of patients with glioblastoma, but its clinical application is restricted due to drug resistance...The nuclear factor of activated T cell isoform c3 (NFATc3), which acts as a transcriptional factor, bridges TRPC5 activity to P-gp induction. In conclusion, these results demonstrate the functional role of the TRPC5-NFATc3-P-gp signalling pathway in TMZ resistance in glioblastoma cells.
Journal
|
NFATC3 (Nuclear Factor Of Activated T Cells 3)
|
temozolomide
1m
P=N/A, N=120, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Initiation date: Jun 2021 --> Dec 2021
Clinical • Trial initiation date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MGMT (6-O-methylguanine-DNA methyltransferase)
|
IDH1 mutation
|
temozolomide
1m
P2, N=62, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2023 --> Jul 2027 | Trial primary completion date: Jul 2022 --> Jul 2025
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
BRAF (B-raf proto-oncogene)
|
Braftovi (encorafenib) • Mektovi (binimetinib)
1m
Collectively, these results provide a new way to stratify glioblastoma patients that uses network features as biomarkers to predict survival. They also identify new potential therapeutic interventions, underscoring the value of analyzing gene regulatory networks in individual cancer patients.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden)
1m
We demonstrate marked suppression in tumor growth upon targeting of HDAC1 and identify compensatory pathways that provide insights into combination therapies for GBM. Our study highlights the importance of HDAC1 in GBM and the need to develop isoform-specific drugs.
Journal
|
HDAC1 (Histone Deacetylase 1) • HDAC2 (Histone deacetylase 2)
1m
Finally, using an organoid-based glioma invasion assay and brain xenografts in mice, we establish that ciliogenesis-induced differentiation can prevent the infiltration of GSCs into the brain. Our findings illustrate a role for cilium as a molecular switch in determining GSCs' fate and suggest cilium induction as an attractive strategy to intervene in GSCs proliferation.
Journal
|
PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
1m
 Time to irradiation had no significant influence on OS of the entire cohort. Nevertheless, a statistically nonsignificant survival prolongation could be observed in patients with residual tumor volume > 2 mL when admitted to radiotherapy within 28 days after surgery.
Clinical • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide
1m
The aim of this study was the preparation of solid lipid nanoparticles (SLN) formed from cetyl palmitate with having targeting molecules for monocarboxylate transporter-1 (MCT-1): β-hydroxybutyric acid and anticancer agents: carmustine (BCNU) and temozolomide (TMZ) for enhanced anti-proliferation against glioblastoma multiforme (GBM). In addition, targeted nanoparticles were more uptaken by MCT-1 expressing brain cells. This study indicated that BCNU and TMZ loaded SLNs could act as a useful anticancer system for targeted GBM therapy.
Journal
|
MCT1 (SLC16A1)
|
temozolomide • carmustine
1m
According to fluorescence microscopy, FAM-ME07 interacts directly with the receptors on A431 cells, followed by its internalization into the cytoplasm and translocation to the nucleolus; this finding opens a possibility of ME07 application as an escort aptamer for a delivery of therapeutic agents into tumor cells. FAM-ME07 efficiently stains sections of GBM clinical specimens, which enables an identification of EGFR-positive clones within a heterogeneous tumor; and providing a potential for further studying animal models of GBM.
Journal
|
EGFR (Epidermal growth factor receptor)
1m
We highlight the progress in metabolic applications for glioma diagnosis and therapy, and present a map that streamlines the rewired glioma metabolism. The map illustrates the altered reactions in central carbon and nitrogen metabolism that drive glioma biology, and represent metabolic vulnerabilities with translational potential.
Review • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation
1m
Overall, the work has confirmed Cav-1 can serve as an independent prognostic marker in GB, but also augment prognosis when used in combination with a panel of biomarkers or clinicopathologic parameters. Moreover, Cav-1 appears to be linked to many signalling entities within the GB tumour and as such this work begins to substantiate Cav-1 or its associated signalling partners as candidate target for GB new drug discovery.
Clinical • Journal
|
CAV1 (Caveolin 1)
|
CAV1 expression
1m
Released &lsqb; I]ITdU follows the thymidine salvage pathway ending in its incorporation into the DNA of tumor cells. With this concept, a highly efficient strategy for intracellular delivery of radiopharmaceuticals across the challenging BBB is presented.
Journal
|
MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9)
1m
P=N/A, N=4303, Completed, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine | Active, not recruiting --> Completed | Trial completion date: Mar 2021 --> Aug 2021 | Trial primary completion date: Jan 2021 --> Jul 2021
Trial completion • Trial completion date • Trial primary completion date
|
NF1 (Neurofibromin 1)
1m
Furthermore, we speculate that this molecule could form part of the microvesicles that favor abnormal tumor vasculature. Based on the studies presented, this review proposes Netrin-1 as a novel biomarker for GBM progression and vascularization.
Review • Journal
|
NTN1 (Netrin 1)
1m
In addition, NMD inhibition also inhibits tumor growth in a MDM2 overexpressing xenograft tumor model. These results identify NMD inhibition as a novel therapeutic strategy for restoration of p53 function in p53-deficient tumors bearing MDM2 overexpression or p53 mutations downstream of exon 9, subgroups which comprise approximately 6% of all cancers.
Journal
|
MDM2 (E3 ubiquitin protein ligase)
|
TP53 mutation • TP53 expression • MDM2 overexpression
1m
Overexpression of USP5 could significantly extend the half-life of CyclinD1, while knockdown of USP5 decreased the protein level of CyclinD1, which could be restored by proteasome inhibitor MG-132...Taken together, these findings demonstrate that USP5 plays a critical role in tumorigenesis and progression of GBM by stabilizing CyclinD1 protein. Targeting USP5 could be a potential therapeutic strategy for GBM.
Journal
|
CCND1 (Cyclin D1)
|
MG132
1m
This is the first preclinical investigation into the effects of combination checkpoint blockade with anti-PD-1 and anti-BTLA treatment in GBM. We also show a direct effect on activated immune cell populations such as CD4+ and CD8 + T cells and immunosuppressive regulatory T cells through this combination therapy.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • BTLA (B And T Lymphocyte Associated) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
|
IFNG expression • CD4 expression
1m
In this study, a novel prognostic model based on three pyroptosis-related genes is constructed and used to predict the prognosis of GBM patients. The model can accurately and conveniently predict the 1-, 3-, and 5-year OS of GBM patients.
Journal • Gene Signature
|
CASP9 (Caspase 9)
1m
The levels of SNHG6 and Notch1 were also found elevated in Grade IV glioma patients (n = 4) relative to Grade II glioma patients (n = 5). These results identify SNHG6 and Notch1 as valid targets for glioma therapy.
Journal
|
NOTCH1 (Notch 1) • SOX2
1m
Of all inhibitors tested, HDACi (panobinostat and romidepsin) showed the potential to increase the expression of ERβ in GBM cells. In orthotopic GBM model, combination therapy of panobinostat and LY500307 enhanced survival of tumor-bearing mice. Our results suggest that the combination therapy of HDACi and LY500307 provides therapeutic utility in overcoming the suppression of ERβ expression that commonly occurs in GBM progression.
Journal • Epigenetic controller
|
ER (Estrogen receptor)
|
ER expression
|
Farydak (panobinostat) • Istodax (romidepsin) • erteberel (LY500307)
1m
The crude model indicated linearity between methylation percent and survival rate; an increase of 10% of methylation resulted in a reduction of risk of death by 20% (p = 0.004). ROC analysis determined 21% as the optimal cutoff point for MGMT methylation status by pyrosequencing.
Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
temozolomide
1m
Our study reveals a newly non-metabolic IDO-mediated enhancement of CFH expression and provides a new therapeutic target in patients with GBM.
Journal • IO biomarker
|
IDO1 (Indoleamine 2,3-dioxygenase 1)
|
IDO1 expression
1m
Finally, inhibition of phosphorylation of Src and FAK significantly reversed the augmentation of invasion and migration caused by PPFIBP1 overexpression in GBM cells. In conclusion, these findings uncover a novel mechanism of glioma invasion and identify PPFIBP1 as a potential therapeutic target of glioma.
Journal
|
PPFIBP1 (PPFIA Binding Protein 1) • MAPK8 (Mitogen-activated protein kinase 8)
1m
Studies confirmed that the G5-BGG/pDNA complex remained integrated in the hydrogel and was sustainably released for up to 7 days. In an in vivo orthotopic U87MG postoperative tumor model, G5-BGG/shRNA871-loaded hydrogel combined with temozolomide downregulated CD47 protein expression, increased macrophage infiltration into residual tumors, and significantly prolonged the survival time of mice, indicating potential applications for glioblastoma treatment.
Journal
|
CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
|
temozolomide
1m
P2, N=28, Recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Clinical • New P2 trial
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
Focus V (anlotinib) • penpulimab (AK105)
1m
We developed and translated [F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.
Clinical • Journal
|
PKM (Pyruvate Kinase M1/2)
1m
In vitro experiments showed that silencing RIOK1 inhibited the proliferation, migration, and invasion of glioma cell lines by suppressing AKT and c-Myc expression. These results indicate that the RIOK1-AKT1 axis could play an important role in GBM progression.
Clinical • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
|
MYC expression
1m
Hence, an additive effect of combined treatment in MGMT negative canine glial tumour cell lines in vitro was detected. This motivates to further investigate the association between treatment resistance and MGMT, such as MGMT promoter methylation status.
Preclinical • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
MGMT promoter methylation
|
temozolomide
1m
Rotating magnetic fields produced by a new noninvasive device selectively kill cultured human glioblastoma and non-small cell lung cancer cells by raising intracellular reactive oxygen species, but not normal human tissue cells.
Journal
|
CASP3 (Caspase 3)
1m
Furthermore, SOX2-OT activated ERK signaling pathway in GBM cells. SOX2-OT regulated miR-192-5p/RAB2A axis and ERK pathway to promote GBM cell growth.
Journal
|
SOX2 • YBX1 (Y-Box Binding Protein 1) • MIR192 (MicroRNA 192)
1m
Eventually, rescue assays validated PITPNA-AS1 sponged miR-223-3p to promote EGFR expression, thus activating PI3K/AKT signaling pathway to accelerate proliferation and inhibit apoptosis of GBM cells. Overall, PITPNA-AS1 played an oncogenic role in glioblastoma which might be developed as a potential biomarker for glioblastoma diagnosis and treatment in the future.&lsqb;Figure: see text].
Journal
|
EGFR (Epidermal growth factor receptor) • MIR223 (MicroRNA 223)
|
EGFR expression
1m
HIF1α orchestrates expression of PDGF-D and PDGFRα for constitutive activation of AKT pathway and is crucial for GBM malignancy. Therefore, therapies targeting HIF1α should provide an effective treatment for GBM.
Journal
|
PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • HIF1A (Hypoxia inducible factor 1, alpha subunit)
|
FOLR1 expression • HIF1A expression • PDGFRA expression
|
echinomycin
1m
Compound 7l was further investigated for its in-cell enzymatic HO-1 activity, expression levels, and effects on cell invasion and vascular endothelial growth factor (VEGF) extracellular release. The obtained data suggest that 7l can reduce cell invasivity acting through modulation of HO-1 expression.
Preclinical • Journal
|
HMOX1 (Heme Oxygenase 1)
1m
In this article we present genomic and pre-clinical data that supports telomerase as a potential "Achilles' heel" for glioblastoma. We also summarize prior experience with anti-telomerase agents and potential new approaches to tackle this target.
Journal
|
TERT (Telomerase Reverse Transcriptase)
|
TERT promoter mutation • TERT mutation
1m
The present study was performed on a less numerous but ethnically homogeneous population. Hence, future investigations in larger and multiethnic groups are needed to strengthen these results.
Journal
|
AURKA (Aurora kinase A) • AURKB (Aurora Kinase B) • PLK1 (Polo Like Kinase 1)
1m
There was a statistically significant difference in OS of 85% at 12 months for the subgroup of patients "HIF-1α negative IDH1 positive" p = 0.038, the unadjusted analysis showed that the group "HIF-1α positive, IDH1 positive" was a poor prognostic factor, the HR was 0.08 (95% CI: 0.009-0.756, p = 0.027). Patients with negative HIF-1α expression and positive IDH1 expression have a better prognosis, suggesting that these two biomarkers may be useful in the search for new approaches for targeted therapy in glioblastoma.
Clinical • Journal
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit)
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TP53 expression • HIF1A expression
1m
Importantly, we establish that galectin1 forms a complex with the transcription factor HOXA5 to reprogram the BTSC transcriptional landscape. Our data unravel an oncogenic signaling pathway by which the galectin1/HOXA5 complex maintains BTSCs and promotes glioblastoma.
Journal
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STAT3 (Signal Transducer And Activator Of Transcription 3)
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STAT3 expression
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OTX-008
1m
P1/2, N=113, Recruiting, Virginia Commonwealth University | N=81 --> 113
Enrollment change
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EGFR (Epidermal growth factor receptor)
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EGFR mutation
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Nerlynx (neratinib) • sodium valproate
1m
We also uncovered a paralogous synthetic lethal mechanism behind a genetic interaction between STAG2 and the iron regulatory gene IREB2 Finally, investigation of an unusually strong context-dependent genetic interaction in HAP1 cells revealed factors that could be important for alleviating cohesin loading stress. Together, our results reveal new facets of STAG2 and cohesin function across a variety of genetic contexts.
Journal • Synthetic lethality
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STAG2 (Stromal Antigen 2)
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STAG2 mutation
1m
In silico analysis showed that taxifolin can bind to the rapamycin binding site of mTOR and the catalytic site of PI3K (p110α)...Lastly, we showed that taxifolin suppressed tumors in mice; stimulated expression of autophagy-related genes LC3B-II, Atg7, atg12, and Beclin-1; and inhibited expression of fatty acid synthesis-related genes C/EBPα, PPARγ, FABP4, and FAS. Our observations suggest that taxifolin is potentially a valuable drug for treating GBM.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • ATG12 (Autophagy Related 12) • ATG7 (Autophagy Related 7) • BECN1 (Beclin 1) • FABP4 (Fatty Acid Binding Protein 4)
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sirolimus
1m
Our study determined that weakness and memory loss/confusion were the symptoms that predicted diminished survival, and weakness alone was the symptom that predicted an earlier diagnosis. This study further elucidates the complexities of glioblastoma and provides clinicians with more data for their patients when discussing prognostication after diagnosis of glioblastoma.
Clinical • Journal
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PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
1m
Taken together, these results suggest that miRNA-451 could regulate the NF-κB signaling pathway by targeting IKKβ, which inhibits glioma cell growth in vitro and in vivo. Therefore, this study may provide novel insight into miRNA-451-targeted therapy for glioma.
Journal
|
CCND1 (Cyclin D1) • MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9) • PCNA (Proliferating cell nuclear antigen) • RELA (RELA Proto-Oncogene)
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CCND1 expression
1m
P1, N=305, Recruiting, Boehringer Ingelheim | Trial completion date: Dec 2021 --> Jul 2023 | Trial primary completion date: Aug 2021 --> Mar 2023
Clinical • Trial completion date • Trial primary completion date • Combination therapy • PD(L)-1 companion diagnostic
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression
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BI 836880 • ezabenlimab (BI 754091)
1m
PK exposure was similar to that observed in adults. Conclusions Repotrectinib demonstrated encouraging clinical activity in pediatric patients with ROS1+ and NTRK+ tumors including patients with CNS disease, and a favorable safety profile similar to that seen in adults.
Clinical • P1/2 data
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ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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ALK fusion • NTRK fusion
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repotrectinib (TPX-0005)
1m
Overall, the study provided that lncRNA CRNDE is a reliable clinical predictor of outcome and prognosis and a potential biomarker for predicting TMZ treatment response in GBM by modulating the autophagy through PI3K/Akt/mTOR pathway and ABCG2 expression which may be a novel therapeutic target for regulating TMZ sensitivity to GBM.
Journal
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ABCG2 • ATG5 (Autophagy Related 5) • BECN1 (Beclin 1)
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temozolomide
1m
Conventionally fractionated RT with concomitant chemotherapy could safely be applied in multifocal high-grade glioma in this case series despite large irradiation treatment fields.
Clinical • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase)
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Avastin (bevacizumab) • temozolomide • lomustine
1m
The results of the dual luciferase assay supported a direct interaction of Hsa-miR-11181 with the 3' UTR sequences of the AKT2 and TGFBR1 genes. Overall, our data suggest that miR-1118 is a potential molecular biomarker for discrimination of glioma brain tumours from other brain tumour types.
Journal
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AKT2 (V-akt murine thymoma viral oncogene homolog 2) • EGF (Epidermal growth factor)
1m
Moreover, miR-23a overexpression reversed the inhibitory effects of circPTK2 overexpression on cell behaviors. CircPTK2 might suppress cancer cell invasion and migration by inhibiting the maturation of miR-23a.
Journal
|
MIR23A (MicroRNA 23a)
1m
Here, we review the physiological role of EIF4A3 and the potential association between EIF4A3 overexpression and tumorigenesis. We also evaluate the protein's potential utility as a diagnosis biomarker, therapeutic target, and prognosis indicator, hoping to provide new ideas for future research.
Review • Journal
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GPX4 (Glutathione Peroxidase 4)
1m
In conclusion, HOXB7 is an independent predictor of poor prognosis in all grade gliomas. Additionally, HOXB7 is also a highly sensitive and specific indicator to differentiate oligodendroglioma from astrocytoma.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
2ms
P2, N=37, Recruiting, Northwell Health | Trial completion date: May 2022 --> May 2025 | Trial primary completion date: May 2021 --> May 2024
Trial completion date • Trial primary completion date
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EGFR (Epidermal growth factor receptor)
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EGFR overexpression
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Erbitux (cetuximab)
2ms
Moreover, treatment of glioblastoma cells with the PR_b liposomes encapsulating miR-603/PEI sensitized the cells to ionizing radiation (IR), a standard of care treatment for glioblastomas. These results suggest that PR_b-functionalized PEGylated liposomes encapsulating miR-603/PEI complexes hold promise as a therapeutic platform for glioblastomas.
Clinical • Journal
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IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1) • FN1 (Fibronectin 1)
2ms
Our results show the ability of deep learning in learning a complex association of risk factors. Moreover, the remarkable performance of the deep-learning-based survival model could be promising to support decision-making systems in personalized medicine for patients with GBM.
Clinical • Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
2ms
GCG is an uncommon tumour accounting for 2-5% of GB. Genetically, GCG is considered a variant of IDH-wild type GB but with high frequency of TP53 mutation and lack of EGFR amplification. Macroscopically it is well limited and histologically it is characterized by the presence of plentiful bizarre multinucleated giant cells.
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • GFAP (Glial Fibrillary Acidic Protein)
|
TP53 mutation • EGFR mutation • EGFR amplification
2ms
Current molecular evidence supports a monoclonal origin of both glial and sarcomatous components, the latter usually presenting as a fibrosarcoma-like proliferation. Osteoid and chondroblastic differentia- tion are exceptionally rare morphologies of this uncommon GBM variant, with only a few described cases in SGS. SGS's patients harbour an unfavourable prognosis, and further research is required to better understand this tumour.
GFAP (Glial Fibrillary Acidic Protein)
2ms
Glioblastomas are heterogeneous tumours. A systematic search for molecular alterations, in particular those of IDH and EGFR, to distinguish primary from secondary glioblastomas and should be im- posed in order to establish a good diagnosis and better management of patients with glioblastoma. The IDH mutation characterizes secondary glioblastomas while the EGFR gene amplification strongly suggests the diagnosis of primary glioblastomas.
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler)
|
EGFR amplification • IDH1 R132H • IDH2 R172K • TP53 expression • IDH2 R172
2ms
Clinical and imaging features of primary CNS lymphoma and glioblastoma are highly variable and sometimes similar, difficult to differentiate, and this is why it is important to recognize this entity in order to avoid misdiagnosis. The morphological evaluation of the pre- sented cases has confirmed the diagnosis and has ensured adequate treat- ment and follow-up. The histopathological and immunohistochemical evaluation played an essential role in establishing the final diagnosis, in order to determinate the neoplastic proliferation line and the subtype of lymphoma.
Clinical
|
CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6) • TNFRSF8 (TNF Receptor Superfamily Member 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • MME (Membrane metallo-endopeptidase)
|
CD20 positive
2ms
However, low T2' values, suggesting high amounts of deoxyhemoglobin, were found in samples with elevated vessel densities, but not in samples with increased immunopositivity for LDHA. Taken together, some of our observations were consistent with previous findings but the correlation of quantitative MRI and histologic parameters did not confirm all our pathophysiology-based assumptions.
Journal
|
LDHA (Lactate dehydrogenase A)
2ms
Pre-clinical testing of a microcontroller-based device emitting light of 405 nm wavelength in combination with exposure to 5-ALA (PDT) and the Bcl-2/Bcl-xL inhibitor ABT-263 (navitoclax) was performed in human established and primary cultured glioblastoma cells as well as glioma stem-like cells...This effect can be partly attributed to cytotoxicity and is likely related to a pro-apoptotic shift because of an increased Noxa/Mcl-1 ratio. The results of this study warrant further investigation.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)
|
navitoclax (ABT 263)
2ms
Specifically, we will describe PACAP ability to interfere with GBM cell proliferation, as well as the tumoral microenvironment. Considering its anti-oncogenic role in GBM, synthesis of PACAP agonist molecules may open new perspectives for combined therapy to existing gold standard treatment.
Review • Journal
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ADCYAP1 (Adenylate Cyclase Activating Polypeptide 1)
2ms
Herein, we described a long-term glioblastoma 3D model system that could be particularly helpful for drug testing and treatment optimization.
Preclinical • Journal
|
MGMT (6-O-methylguanine-DNA methyltransferase) • ABCB1 (ATP Binding Cassette Subfamily B Member 1)
|
temozolomide
2ms
Our evidence suggests that modulation of the SHH effector smoothened (SMO), by using a known agonist (i.e., purmorphamine) and a known antagonist (i.e., cyclopamine), affects the CX43 expression levels and therefore the related functions...Importantly, inhibition of CX43 channels was able to prevent SMO-induced effects. SHH pathway and CX43 interplay acts inducing tumorigenic program and supporting cell migration, likely representing druggable targets to develop new therapeutic strategies for GBM.
Journal
|
SMO (Smoothened Frizzled Class Receptor) • GJA1 (Gap Junction Protein Alpha 1)
|
GJA1 expression
|
cyclopamine
2ms
Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy.
Journal
|
CD44 • MMP2 (Matrix metallopeptidase 2) • VIM (Vimentin) • ADCYAP1 (Adenylate Cyclase Activating Polypeptide 1) • MMP9 (Matrix metallopeptidase 9)
|
VIM expression
2ms
GBM cells develops resistance against chemotherapeutic agent, temozolomide (TMZ), which leads to the failure in treatment strategies...The combinatorial drug showed promising anti-tumor efficacy in GBM xenograft model by reducing the tumor volume, suggesting it as an alternative drug to TMZ. Our findings indicate the coordinated administration of THTMP + T0 as an efficient therapy for inhibiting GBM cell proliferation.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • XIAP (X-Linked Inhibitor Of Apoptosis)
|
BCL2 expression
|
temozolomide
2ms
Finally, by qRT-PCR, the modulation of Wnt/β catenin, FGF, and TGFβ/SMAD signaling pathways in PN- and MES-GSCs was reported. Overall, our results provide new evidence regarding Runx1/Aml1 isoform overexpression and modulation in TRP channel expression during gliomagenesis, thus offering new directions for glioblastoma therapy.
Preclinical • Journal
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RUNX1 (RUNX Family Transcription Factor 1)