|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
In this report, we evaluate the clinical characteristics and outcomes of patients with prostate cancer and CDK12 mutation in their tumors.
|
31640893 |
2020 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Furthermore, CDK12 kinase activity inhibition facilitates anticancer efficacy of trastuzumab in HER2<sup>+</sup> tumors, and mice bearing trastuzumab-resistant HER2<sup>+</sup> tumor show sensitivity to an inhibitor of CDK12.
|
31468695 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
EWS/FLI Confers Tumor Cell Synthetic Lethality to CDK12 Inhibition in Ewing Sarcoma.
|
29358035 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
An increasing number of studies point to CDK12 inhibition as an effective strategy to inhibit tumour growth, and synthetic lethal interactions have been described with MYC, EWS/FLI and PARP/CHK1 inhibition.
|
30104286 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The mRNA levels of CDK12, PALB2 and XPF inversely associated with the <i>in vivo</i> DDP antitumor activity; higher CDK12 mRNA levels were associated with a higher recurrence rate in ovarian patients with low residual tumor.
|
29872499 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
This observation suggests that the mutational status of CDK12 may predict sensitivity to targeted treatments against BRCAness, such as PARP1 inhibitors, and that CDK12 inhibitors may induce sensitization of HR-competent tumours to these treatments<sup>6,7,10,11</sup>.
|
30487607 |
2018 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
CDK12 mutant cases are associated with elevated neoantigen burden ensuing from fusion-induced chimeric open reading frames and increased tumor T cell infiltration/clonal expansion.
|
29906450 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Therefore, we suggest CHK1 inhibition as a strategy for targeting BRCA1- or CDK12-deficient tumors.
|
29025359 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The positive correlation observed between this polymorphism and age, grade and residual tumor may explain why the CDK12 variant was not confirmed as an independent prognostic factor in multivariate analysis.The importance of CDK12 polymorphism as possible prognostic biomarker need to be confirmed in larger ovarian cancer cohorts, and possibly in other cancer population responsive to platinum agents.
|
27905519 |
2016 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We propose that CDK12 is a tumor suppressor of which the loss-of-function mutations may elicit defects in multiple DNA repair pathways, leading to genomic instability underlying the genesis of the cancer.
|
25712099 |
2015 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Notably, integration of the list of candidate sensitivity genes with data from tumor DNA sequencing studies identified CDK12 deficiency as a clinically relevant biomarker of PARP1/2 inhibitor sensitivity.
|
24240700 |
2014 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12.
|
22544022 |
2012 |