|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
As a specific small-molecule inhibitor of the Wee1 tyrosine kinase, AZD1775 has previously shown potent antitumor effect on multiple types of cancer in various preclinical studies and clinical trials.
|
31427973 |
2019 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Likewise, the immune responses of T cells neither improved nor suppressed when dually co-stimulated PBMCs were exposed to the cancer cells with silenced WEE1.
|
26881506 |
2016 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
DNA damage checkpoint kinases ATR and WEE1 are among key regulators of DNA damage response pathways protecting cells from replication stress, a hallmark of cancer that has potential to be exploited for therapeutic use.
|
31123088 |
2019 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA-damaging agents.Mol Cancer Ther; 15(7); 1669-81.©2016 AACR.
|
27196765 |
2016 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We here focus on the proteins ATM, ATR, CHK1 and WEE1, reviewing their roles in the DNA damage response and as targets in cancer therapy.
|
28961555 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Wee1 inhibition by small interfering RNA was demonstrated to significantly restrain cancer cell proliferation and sensitize the p53 mutant colonic cancer cell lines HT29 and SW480 to the effect of treatment with ionizing radiation.
|
29257266 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
WEE1 inhibition also results in evident anti-tumor effects in several human tumor cells including colon cancer cells, suggesting WEE1 as a potential therapeutic target for the treatment of cancer.
|
28599436 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001), Ki67 (p<0.0001), Cyclin D3 (p = 0.001), p21(Cip1/WAF1) (p = 0.003), p53 (p = 0.025).
|
22719872 |
2012 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Thus, our work highlights the importance of improved therapeutic strategies for patients with various cancer types and may explain why some patients respond better to WEE1 inhibitors.
|
30190546 |
2019 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
TIMELESS depletion in combination with Wee1 or CHK1 inhibition causes an additive decrease in cancer cell metabolic capacity with limited effects in non-transformed human colon epithelial cells.
|
30629587 |
2019 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Our data indicate that Wee1 inhibition provides a new approach for treatment of multiple human malignancies.
|
19887545 |
2009 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
WEE1 is overexpressed in various cancer types, including glioblastoma and breast cancer.
|
21562035 |
2011 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Development of Potent Pyrazolopyrimidinone-Based WEE1 Inhibitors with Limited Single-Agent Cytotoxicity for Cancer Therapy.
|
29883531 |
2018 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In conclusion, the clinical combination of a Chk1 inhibitor and a Wee1 inhibitor holds promise as an effective treatment strategy for cancer.
|
21892012 |
2011 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Upregulation of Myt1 Promotes Acquired Resistance of Cancer Cells to Wee1 Inhibition.
|
31594837 |
2019 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Accordingly, the WEE1 inhibitor AZD1775 (previously MK-1775) is currently under evaluation in clinical trials for cancer in combination with chemotherapy.
|
28557434 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Various studies have indicated that WEE1 could be a good target for cancer therapy.
|
24377575 |
2014 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Molecular Pathways: Targeting the Protein Kinase Wee1 in Cancer.
|
28442503 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
ATR and Wee1 inhibition had a higher synergistic effect in cancer stem cells than in bulk cancer cells, compensating for the lower sensitivity of cancer stem cells to the individual drugs.
|
30645202 |
2019 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The selective Wee1 inhibitor MK-1775 has demonstrated promising results when combined with DNA damaging agents, and more recently with CHK1 inhibitors in various malignancies.
|
25458954 |
2015 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here, we investigated how WEE1 inhibition could be best exploited for cancer therapy by performing a functional genetic screen to identify novel determinants of sensitivity to WEE1 inhibition.
|
25673822 |
2015 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Mechanistically, we show that inhibition of mTOR potentiates WEE1 inhibition by abrogating compensatory activation of DNA repair, exacerbating DNA damage in <i>KRAS</i>-mutant NSCLC, and that this effect is due in part to reduction in cyclin D1.<b>Conclusions:</b> These findings demonstrate that compromised DNA repair underlies the observed potent synergy of WEE1 and mTOR inhibition and support clinical evaluation of this dual therapy for patients with <i>KRAS</i>-mutant lung cancers.<i>Clin Cancer Res; 23(22); 6993-7005.©2017 AACR</i>.
|
28821559 |
2017 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
ATM, ATR, CHK1, CHK2 and WEE1 inhibitors in cancer and cancer stem cells.
|
30108746 |
2017 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Wee1 is overexpressed in pediatric HGGs, with increasing expression positively correlated with malignancy (P = .007 for grade III + IV vs I + II) and markedly high expression in DIPG.
|
24305702 |
2014 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Several studies in solid tumors identified high expression of WEE1 kinase as a poor prognostic factor and reported its role as a cancer-conserving oncogene that protects cancer cells from DNA damage.
|
30068368 |
2018 |