|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
The findings of this study provide the first evidence of CDK4 gene amplification in breast cancer and suggest that CDK4 gene amplification appears to be of importance in the pathogenesis of a subset of sporadic breast cancer.
|
9916925 |
1999 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancers.
|
11023200 |
2000 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
We report that the ability of cyclin D1 to activate cyclin-dependent kinase CDK4 underlies the critical role for cyclin D1 in breast cancer formation.
|
16413469 |
2006 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991
|
19874578 |
2009 |
|
Malignant neoplasm of breast
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Cyclin-dependent kinase 4-mediated phosphorylation inhibits Smad3 activity in cyclin D-overexpressing breast cancer cells.
|
20736297 |
2010 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
These data support further development of ER downregulators and CDK4 inhibitors, and their combination with PI3K inhibitors for treatment of antiestrogen-resistant breast cancers.
|
22049316 |
2011 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
T1 caused cell cycle arrests of both estrogen-dependent and estrogen-independent cell lines associated with alterations of cyclinD, CDK4 and cyclinB, and induced breast cancer cell apoptosis associated with upregulation of c-PARP and downregulation of survivin and Aurora A.
|
22485147 |
2012 |
|
Malignant neoplasm of breast
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
CDK4 expression did not correlate with cyclin D1 expression or the survival data. p16 expression was associated with Human Epidermal Growth Factor Receptor 2 (HER2) negativity and increased breast cancer-specific survival and disease-free survival.
|
23336272 |
2013 |
|
Malignant neoplasm of breast
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors.
|
25002028 |
2014 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
CDK4 inhibition and doxorubicin mediate breast cancer cell apoptosis through Smad3 and survivin.
|
25006666 |
2014 |
|
Malignant neoplasm of breast
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
MiR-124 inhibits cell proliferation in breast cancer through downregulation of CDK4.
|
25731732 |
2015 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this review, we outline the development of CDK inhibitory therapy in breast cancer, including the initial experience with the pan-CDK inhibitor flavopiridol and the next generation of oral highly selective CDK4 and CDK6 inhibitors PD0332991 (palbociclib), LEE011 (ribociclib), and LY2835219 (abemaciclib).
|
25876993 |
2015 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
SERDs, SSHs, and the CDK4/6 inhibitor palbociclib were evaluated as single agents or in combination in established cellular and animal models of endocrine therapy-resistant ESR1(+) breast cancer.
|
25991817 |
2015 |
|
Malignant neoplasm of breast
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Concerning CDK4 gene, 5 mutations were identified and a significant association was observed between CDK4 gene mutations and breast cancer.
|
26416047 |
2015 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
Nek2 is a mitotic kinase commonly upregulated in breast cancers and a critical regulator of Cdk4- or E2F-mediated CA.
|
26512919 |
2015 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation.
|
26540629 |
2015 |
|
Malignant neoplasm of breast
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
FDA approval of the CDK4/6 inhibitor palbociclib used with the aromatase inhibitor letrozole for breast cancer treatment highlights long-sought success.
|
26658964 |
2016 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, recent preclinical and phase I/II clinical studies using a novel, oral, reversible CDK4/6 inhibitor, palbociclib (PD-0332991), have validated the role of CDK4/6 as a potential target in estrogen receptor-positive (ER+) breast cancers.
|
26857361 |
2016 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
This article reviews the rationale for targeting cyclin D-CDK 4/6 in hormone receptor-positive (HR+) breast cancer, provides an overview of the available preclinical and clinical data with CDK 4/6 inhibitors in breast cancer to date, and summarizes the main features of ongoing clinical trials of these new agents in breast cancer.
|
26896604 |
2016 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
We also discuss the application of genome-wide genetic screening efforts to gain insight into synthetic lethal interactions of CDK4/6 inhibitors in breast cancer for the development of more effective combination therapies.
|
26923330 |
2016 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
In particular, the combination of CDK4/6 inhibitors with endocrine therapy, such as palbociclib's recent first-line approval in combination with letrozole, is expected to transform the treatment of HR+ breast cancer.
|
27017286 |
2016 |
|
Malignant neoplasm of breast
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
While specific kinase inhibitors have had success in the clinic, including the CDK4/6 inhibitor palbociclib in combination with aromatase inhibitors in luminal breast cancer, patients often become resistant to treatment.
|
27186656 |
2017 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC).
|
27336726 |
2016 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib.
|
27634906 |
2016 |
|
Malignant neoplasm of breast
|
0.100 |
Biomarker
|
disease |
BEFREE |
Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway.
|
27649142 |
2016 |