|
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 |
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 |
Treatment with non-toxic concentrations of a Chk1 inhibitor (PF-00477736) and a Wee1 inhibitor (MK-1775) confirmed the marked synergistic effect in various human cancer cell lines (breast, ovarian, colon, prostate), independently of the p53 status.
|
22713237 |
2012 |
|
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 |
Preclinical studies have elucidated the role of wee1 in DNA damage repair and the stabilization of replication forks, supporting the validity of wee1 inhibition as a viable therapeutic target in cancer.
|
24013427 |
2013 |
|
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 |
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 |
WEE1, a mitotic inhibitor kinase, regulates the DNA damage repair pathway, and therapeutic inhibition of WEE1 in combination with chemotherapy is currently in early phase trials for the treatment of cancer.
|
24536047 |
2014 |
|
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 |
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 |
AlteredExpression
|
group |
BEFREE |
Over-expression of WEE1 in glioblastomas (GBMs) and some other cancers has been shown.
|
27072241 |
2016 |
|
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 |
Finally, we demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes.
|
28262781 |
2017 |
|
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 |
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 |
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 |
The combination of vorinostat and AZD1775 inhibits tumor growth and angiogenesis <i>in vivo</i> in an orthotopic mouse model of oral cancer and prolongs animal survival.<b>Conclusions:</b> Vorinostat synergizes with AZD1775 in HNSCC cells with mutant p53 <i>in vitro</i> and <i>in vivo</i> A strategy combining HDAC and WEE1 inhibition deserves further clinical investigation in patients with advanced HNSCC.<i>Clin Cancer Res; 23(21); 6541-54.©2017 AACR</i>.
|
28790110 |
2017 |
|
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 |
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 |
These data indicate that the epigenetic repression of <i>IDH2</i> by WEE1/pY37-H2B circuit may be a hitherto unknown mechanism of global 5-hmC loss observed in human malignancies.
|
29290954 |
2017 |
|
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 |
Based on a series of signaling pathways initiated by Wee1, Wee1 has been recognized as a potential target for cancer therapy.
|
30052133 |
2019 |