|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
We conducted a phase Ib study (NCT02345824) to determine whether ribociclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), penetrates tumor tissue and modulates downstream signaling pathways including retinoblastoma protein (Rb) in patients with recurrent glioblastoma (GBM).
|
31399936 |
2019 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma.
|
31307887 |
2019 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here, effects of CDK4/6 inhibitors on various kinds of GBM cell lines are investigated and the functional mechanisms are identified.
|
31787897 |
2019 |
|
Glioblastoma Multiforme
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The purpose of this work is to elucidate the in vivo role of cytoplasmic Ccnd1-Cdk4 activity in the dissemination of GBM.
|
30957234 |
2019 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Collectively, these findings demonstrate that the activation of c-Met/TrkA-B pathways is a novel mechanism involved in therapeutic resistance of GBM to CDK4/6 inhibition and that dual inhibition of c-Met/Trk with CDK4/6 should be considered in future clinical trials.<b>Significance:</b> CDK4/6 inhibition in glioblastoma activates the c-Met and TrkA-B pathways mediated by NF-κB and can be reversed by a dual c-Met/Trk inhibitor.<i></i>.
|
29844123 |
2018 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Characterization of diverse immune responses will facilitate patient stratification and improve personalized immunotherapy in the future.<b>Significance:</b> This study utilizes a computational approach to characterize the immune environments in glioblastoma and shows that glioblastoma immune microenvironments can be classified into three major subgroups, which are linked to typical glioblastoma alterations such as IDH mutation, NF1 inactivation, and CDK4-MARCH9 locus amplification.<b>Graphical Abstract:</b> http://cancerres.aacrjournals.org/content/canres/78/19/5574/F1.large.jpg <i></i>.
|
29921698 |
2018 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the present study, we investigate efficacy of combination of palbociclib, cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and erlotinib, epidermal growth factor receptor (EGFR) inhibitor in GBM cell systems with different p53 status.
|
29508248 |
2018 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis.
|
30470262 |
2018 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here, we designed and synthesized a series of novel CDK4/6 inhibitors with favorable BBB permeability for the treatment of GBM.
|
29247857 |
2018 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
In addition to identifying essential genes already implicated in GBM such as <i>CDK4, KIF11</i>, and <i>RAN</i>, the screen also identified new genes that have not been previously implicated in GBM stem cell biology.
|
28993509 |
2018 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
LTS GB showed frequent chromosomal gains in 4q12 (platelet derived growth factor receptor alpha and KIT) and 12q14.1 (cyclin-dependent kinase 4), and deletion in 19q13.33 (BAX, branched chain amino-acid transaminase 2, and cluster of differentiation 33).
|
27932423 |
2017 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Further increasing the utility of the combination for brain cancers, everolimus significantly increases the brain concentration of palbociclib.<b>Conclusions:</b> Our findings demonstrate that the combination of CDK4/6 and mTOR inhibition has therapeutic potential against GBM and suggest it should be evaluated in a clinical trial.<i></i>.
|
28814434 |
2017 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Hence, our findings support that PIKE amplification or overexpression coordinately acts with CDK4 to drive GBM tumorigenesis.
|
28368413 |
2017 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
CDK4/6 inhibition is more active against the glioblastoma proneural subtype.
|
28903422 |
2017 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Gene expression profiles of three glioma stem cell line samples, three normal astrocyte samples, three astrocyte overexpressing 4 iPSC-inducing and oncogenic factors (myc(T58A), OCT-4, p53DD, and H-Ras(G12V)) samples, three astrocyte overexpressing 7 iPSC-inducing and oncogenic factors (OCT4, H-Ras(G12V), myc(T58A), p53DD, cyclin D1, CDK4(RC24) and hTERT) samples and three glioblastoma cell line samples were downloaded from the ArrayExpress database (accession: E-MTAB-4771).
|
28952134 |
2017 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
On real cancer data, pathTiMEx recapitulates previous knowledge on tumorigenesis, such as the temporal order among pathways which include APC, KRAS, and TP53 in colorectal cancer, while also proposing new biological hypotheses, such as the existence of a single early causal event consisting of the amplification of CDK4 and the deletion of CDKN2A in glioblastoma. pathTiMEx is available as an R package.
|
27936934 |
2017 |
|
Glioblastoma Multiforme
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Pharmacological inhibition or small interfering NTSR1 treatment blocked glioblastoma cell cycle progression in the G1 phase with a concomitantly decreased expression of CDK6, CDK4, and c-Myc.
|
26180082 |
2016 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Suppression of tumorigenicity by microRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme.
|
23707559 |
2013 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our findings demonstrated for the first time that CDK4 was a downstream target of miR-124 and that CDA-2 could radiosensitize Glioblastoma multiforme cells through the MiR-124-CDK4 axis.
|
23761023 |
2013 |
|
Glioblastoma Multiforme
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Collectively, these data support the concept that GBM tumors lacking p16(INK4a) expression and with nonamplified CDK4 and wild-type RB status may be more susceptible to Cdk4/6 inhibition using PD0332991.
|
22711607 |
2012 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
A recent study of CDK4/6 inhibitors in glioblastoma (GBM) xenografts identified retinoblastoma tumor suppressor protein RB1 status as a determinant of tumor therapeutic efficacy.
|
22157621 |
2012 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Gene expression-based prediction of genomic copy number aberrations in the chromosomal region 12q13 to 12q15 that is flanked by MDM2 and CDK4 identified Wnt inhibitory factor 1 (WIF1) as a candidate tumor suppressor gene in glioblastoma.
|
21642372 |
2011 |
|
Glioblastoma Multiforme
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These results highlight the prognostic value of CDK4 amplification and of simultaneous EGFR-p53 alterations in the clinical outcome of patients with primary GBM.
|
19141386 |
2009 |
|
Glioblastoma Multiforme
|
0.100 |
Biomarker
|
disease |
BEFREE |
Other amplified regions containing well-known oncogenes in GBMs were also detected at 7p12 (EGFR), 7q21 (CDK6), 4q12 (PDGFRA), and 12q13-15 (MDM2 and CDK4).
|
17002787 |
2006 |
|
Glioblastoma Multiforme
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
No gene rearrangement or deletion was observed in the p19INK4d gene in these cell lines; however, expression of CDK4 and CDK6 was elevated relative to matched normal brain tissue in eight of 18 GBM tumours (44%).
|
10884881 |
2000 |