Mental Retardation, Autosomal Recessive 2
|
0.910 |
Biomarker
|
disease |
BEFREE |
In subgroup analysis restricted to ≤ mrT2/≤ ypT2 and ≤ pT2 tumors (omitting > mrT2 tumors), the effect of nCRT on recurrence no longer varied over time, indicating that tumor heterogeneity was responsible for the observed increased recurrence hazards ≤ 1 year postsurgery; That is, > mrT2 tumors that were downstaged to ≤ ypT2 after nCRT were responsible for the time-varying effects of nCRT and increased recurrence hazards ≤ 1 year postsurgery.
|
31773520 |
2019 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
Biomarker
|
disease |
MGD |
Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.
|
29459374 |
2018 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
GeneticVariation
|
disease |
UNIPROT |
A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family.
|
28143899 |
2017 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
GeneticVariation
|
disease |
CLINVAR |
Molecular diagnostic experience of whole-exome sequencing in adult patients.
|
26633545 |
2016 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
Biomarker
|
disease |
MGD |
Behavioral characterization of cereblon forebrain-specific conditional null mice: a model for human non-syndromic intellectual disability.
|
21995942 |
2012 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation.
|
18414909 |
2008 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation.
|
18414909 |
2008 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
GeneticVariation
|
disease |
UNIPROT |
A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation.
|
15557513 |
2004 |
Mental Retardation, Autosomal Recessive 2
|
0.910 |
CausalMutation
|
disease |
CLINVAR |
|
|
|
Mental Retardation, Autosomal Recessive 2
|
0.910 |
Biomarker
|
disease |
CTD_human |
|
|
|
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
Here, we show that TC11 does not induce degradation of CRBN's substrates, IKZF1/3 and CK1α, and induces apoptosis of CRBN-silenced MM; this effect was independent of the cereblon (CRBN) pathway, which is involved in the mechanism of action of IMiDs used for the treatment of MM.
|
31653349 |
2020 |
Multiple Myeloma
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
It is suggested that selected germline CRBN allelic variants (rs1714327G > C and rs1705814T > C) affect lenalidomide efficacy in patients with relapsed/refractory MM.
|
31746254 |
2020 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
Taken together, our results, in conjunction with recently published findings, provide a rationale for investigating the efficacy of ARV 825 for MM, use of cereblon as a biomarker for therapy of MM patients, and the combination of ARV 825 with small molecule inhibitors to improve the outcome of MM patients.
|
30606790 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
We also demonstrated that treatment with a pan-PIM kinase inhibitor resulted in increased expression of cereblon, and that knockdown of cereblon via a shRNA lentivirus abolished the effects of PIM kinase inhibition on the degradation of IKZF1 and IKZF3 and myeloma cell apoptosis, demonstrating a central role of cereblon in pan-PIM kinase inhibitor-mediated down-regulation of IKZF1 and IKZF3 and myeloma cell killing.
|
30312729 |
2019 |
Multiple Myeloma
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Emerging evidence suggests that IMiDs can block MEIS2 from binding to CRBN facilitating the subsequent activation of a <sup>CRL4</sup>CRBN<sup>IMiD</sup>-E3-ubiquitin ligase activity and proteasome-mediated degradation of critical substrates regulators of Multiple Myeloma (MM) cell survival and proliferation.
|
30975979 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
Immunomodulatory drugs (IMiDs) including lenalidomide and pomalidomide bind cereblon (CRBN) and activate the CRL4<sup>CRBN</sup> ubiquitin ligase to trigger proteasomal degradation of the essential transcription factors IKZF1 and IKZF3 and multiple myeloma (MM) cytotoxicity.
|
30026574 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
Selected CRBN SNPs may be useful in assessing the probability of AEs in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM.
|
31115923 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
The description of their cereblon-mediated mechanism of action was a hallmark in MM research.
|
30696815 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
We herein report our new generation of multifunctional HDAC6 degraders by tethering selective HDAC6 inhibitor Nexturastat A with CRBN ligand that can synergize with HDAC6 degradation for the antiproliferation of multiple myeloma (MM).
|
31271281 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
Notably, targeting CRL4 has recently emerged as a noval anti-cancer strategy, including thalidomide and its derivatives that bind to the substrate recognition receptor cereblon (CRBN), and anticancer sulfonamides that target DCAF15 to suppress the neoplastic proliferation of multiple myeloma and colorectal cancers, respectively.
|
30602127 |
2019 |
Multiple Myeloma
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
This strategy also appeared to be more broadly applicable as SGC-CBP30 could re-sensitize two resistant HMCLs with low but detectable CRBN expression to lenalidomide, suggesting that targeting CBP/E300 is a promising approach to restore IMiD sensitivity in MM with detectable CRBN expression.
|
30741931 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
Thus, our data argue against the use of CRBN and its downstream targets as predictive biomarkers of IMiD response in MM and confirm clonal evolution patterns during lenalidomide resistance.
|
29718735 |
2019 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
These results indicate that the Cereblon-mediated immunomodulatory properties of lenalidomide are maintained in lenalidomide-refractory MM patients and may contribute to immune-mediated killing of MM cells.
|
30338042 |
2018 |
Multiple Myeloma
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Recently, high expression levels of cereblon (CRBN) and MUM1 have been associated with better response rates in multiple myeloma treated with lenalidomide.
|
28833354 |
2018 |
Multiple Myeloma
|
0.600 |
Biomarker
|
disease |
BEFREE |
More broadly, these findings establish key proteins required for lenalidomide-dependent CRL4<sup>CRBN</sup> function in myeloma and inform potential mechanisms of drug resistance.
|
30042095 |
2018 |