|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
CDK4/6 inhibitors are FDA-approved drugs for estrogen receptor-positive (ER<sup>+</sup>) breast cancer and are being evaluated to treat other tumor types, including <i>KRAS</i>-mutant non-small cell lung cancer (NSCLC).
|
31395685 |
2019 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In conclusion, our findings reveal that miR-34b-3p might function as a tumour suppressor in NSCLC by targeting CDK4 and that miR-34b-3p may, therefore, serve as a biomarker for the diagnosis and treatment of NSCLC.
|
31199581 |
2019 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, mechanistic studies showed that the CDK4-pRB-E2F1 pathway was involved in NSCLC.
|
31190865 |
2019 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, SMARCA4 loss is synthetic lethal with CDK4/6 inhibition both in vitro and in vivo, suggesting that FDA-approved CDK4/6 inhibitors could be effective to treat this significant subgroup of NSCLCs.
|
30718506 |
2019 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These data provide a mechanistic rationale for the combination of a PI3Kα inhibitor and a CDK4/6 inhibitor for the treatment of KRAS-mutated NSCLC.
|
31119047 |
2019 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Necitumumab, an anti-EGFR antibody, and abemaciclib, a CDK4/6 inhibitor, have shown activity in patients with non-small cell lung cancer (NSCLC) and have non-overlapping toxicities.
|
31586771 |
2019 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We demonstrate that <i>KRAS</i>-mutant NSCLC cell lines are initially sensitive to the CDK4/6 inhibitor palbociclib, but readily acquire resistance associated with increased expression of CDK6, D-type cyclins and cyclin E. Resistant cells also demonstrated increased ERK1/2 activity and sensitivity to MEK and ERK inhibitors.
|
30167080 |
2018 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In summary, our study signifies inhibiting the CDK4/6 pathway by abemaciclib in combination with IR as a promising therapeutic strategy to treat NSCLC.<b>Conclusions:</b> Abemaciclib in combination with IR enhances NSCLC radiosensitivity in preclinical models, potentially providing a novel biomarker-driven combination therapeutic strategy for patients with NSCLC.<i></i>.
|
29716919 |
2018 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mechanistically, CDK 4/6 inhibition induces a proapoptotic transcriptional program through suppression of IAPs FOXM1 and Survivin, while simultaneously augmenting expression of SMAC and caspase-3 in an RB-dependent manner.<b>Conclusions:</b> This study uncovers a novel function of RB activation to induce cellular apoptosis through therapeutic administration of a palbociclib and provides a rationale for the clinical evaluation of CDK 4/6 inhibitors in the treatment of patients with NSCLC.<i></i>.
|
29311118 |
2018 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
CDK4/6 inhibition stabilizes disease in patients with p16-null non-small cell lung cancer and is synergistic with mTOR inhibition.
|
30647837 |
2018 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Lower miR-340 expression predicts poor prognosis of non-small cell lung cancer and promotes cell proliferation by targeting CDK4.
|
29935356 |
2018 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the present study, we have investigated the anticancer effects of luteoloside on non-small cell lung cancer (NSCLC) cells and demonstrated that luteoloside effectively inhibited cancer cell proliferation, inducing G<sub>0</sub>/G<sub>1</sub> phase arrest associated with reduced expression of CyclinE, CyclinD1 and CDK4; we further found that treatment with luteoloside did not strongly result in apoptotic cell death in NSCLC (A549 and H292) cells.
|
29024631 |
2017 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Our study demonstrated that Foxk2 played major roles in NSCLC EMT by directly targeting N-cadherin and Snail, we found that Foxk2 regulated NSCLC cell growth by suppressing the expression of cyclin D1 and CDK4, which suggested that Foxk2 might be a multifunctional regulator in NSCLC.
|
28260088 |
2017 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
We used siRNA and pharmacologic inhibition of CDK4 and found that the combination of selumetinib and palbociclib synergistically inhibited RAS-driven NSCLC cases with CDKN2A mutations but not those with wild type CDKN2A.
|
28866094 |
2017 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1).
|
26840018 |
2016 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Collectively, our results suggest that miR-486-5p could not only inhibit NSCLC by downregulating the expression of CDK4, but also be as a promising and potent therapy in the near future.
|
27049724 |
2016 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
MiR-613 induces cell cycle arrest by targeting CDK4 in non-small cell lung cancer.
|
26744345 |
2016 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Ectopic expression of miR-134 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1).
|
27166267 |
2016 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
piR-651 promotes tumor formation in non-small cell lung carcinoma through the upregulation of cyclin D1 and CDK4.
|
27431575 |
2016 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC.
|
26802652 |
2016 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Overexpression of RNF146 in NSCLC cell lines increased the levels of cyclinD1, cyclinE, and CDK4, promoted cell cycle G0/G1-S transitions, and regulated cell proliferation.
|
24454854 |
2014 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Moreover, systemic delivery of MNPsiCDK4 significantly inhibited tumor growth in an A549 NSCLC xenograft murine model, with depressed expression of CDK4 and mutational KRAS status, suggesting the therapeutic promise of MNPsiCDK4 delivery in KRAS mutant NSCLCs via a synthetic lethal interaction between KRAS and CDK4.
|
24496383 |
2014 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
These observations suggest that robust and selective pharmacological inhibition of Cdk4 may provide therapeutic benefit for NSCLC patients carrying K-RAS oncogenes.
|
20609353 |
2010 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The retinoblastoma (RB) tumor suppressor is mutated or functionally inactivated in the majority of human malignancies, and p16(INK4a)-cyclin D1-cyclin-dependent kinase 4-RB pathway aberrations are present in nearly all cases of non-small cell lung cancer (NSCLC).
|
17804741 |
2007 |
|
Non-Small Cell Lung Carcinoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, the up-regulation of the proteins JUN, N-RAS, FOS, cyclin D and cdk4 predicts the growth of NSCLC in nude mice.
|
11788907 |
2002 |