|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Purpose AZD1775 is a first-in-class, potent, and selective inhibitor of WEE1 with proof of chemopotentiation in p53-deficient tumors in preclinical models.
|
27998224 |
2016 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In an orthotopic breast cancer model, tumor-selective synthetic lethality of the combination of bioavailable ATR and Wee1 inhibitors led to tumor remission and inhibited metastasis with minimal side effects.
|
30645202 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma.
|
30323762 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Upregulated WEE1 expression was observed in GIST tissues and correlated with tumor size, mitotic count, and risk grade.
|
31197522 |
2020 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2-M DNA damage checkpoint.
|
31390121 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We have shown that genetic targeting AKT3 or WEE1 can be effective for inhibiting tumor growth in preclinical animal models.
|
28705772 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Consequently, the Wee1 inhibitor together with cytarabine or doxorubicin inhibited tumor growth <i>in vitro</i> and <i>in vivo</i> more effectively, providing a potential new therapy for treating B-cell lymphomas.
|
29217775 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Immunohistochemistry were performed on these tumor samples to analyze IDH1 mutation status and protein expression of WEE1. qRT-PCR, western blotting, transwell assays, and scratch wound healing assays were performed to evaluate the effect of WEE1 knockdown or overexpression in HGG cells.
|
29502292 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In conclusion, the up-regulation of BUB1B, CCNA2, CDC20, CDK1, and WEE1 in tumor tissues are associated with worse OS and DFS in PDAC and is correlated with advanced tumor stage and tumor development.
|
30765611 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Our findings demonstrate that sensitization to chemoradiation by WEE1 inhibition results from inhibition of HR repair and suggest that patient tumors without underlying HR defects would benefit most from this therapy.
|
26585231 |
2015 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
RNAi mediated inhibition of AKT3 and WEE1 synergistically inhibited the viability of melanoma cells leading to a 65-75% decrease in tumor development.
|
28853983 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Thus, inhibiting Wee1, alone or in combination with DNA damaging agents, can kill cancer cells by mitotic catastrophe, a tumor suppressive response that follows mitosis onset in the presence of under-replicated or damaged DNA.
|
31200459 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma orthotopic patient-derived xenografts tumours in vivo.
|
28854174 |
2017 |
|
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Taken together, our data suggest that CHEK1 or WEE1 inhibitors are likely to have greater clinical efficacy in tumors with RAD17 loss-of-function.
|
26437225 |
2015 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Sequential inhibition of PARP and WEE1 limits tumor growth and reduces toxicity in multiple cancers.
|
31227515 |
2019 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The selective WEE1 inhibitor, AZD1775, has shown strong anti-proliferative effects on a variety of tumors.
|
29605721 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
We also demonstrate here that the defects in tumor cell death described in association with very high levels of brachyury could be alleviated <i>via</i> the use of a WEE1 inhibitor.
|
29774202 |
2018 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Among these 6 genes, 3 transcription factors as well as the topoisomerase II alpha and the mitosis inhibitor WEE1Hu gene were significantly suppressed in the tumour cell lines.
|
10446455 |
1999 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Taken together, these mechanistic data demonstrate that although nucleotide depletion is sufficient for radiosensitization by WEE1 inhibition alone, and inhibition of PARP catalytic activity is sufficient for radiosensitization by olaparib alone, PARP1 trapping is required for enhanced radiosensitization by the combination of WEE1 and PARP inhibitors.<b>Implications:</b> This study highlights DNA replication stress caused by nucleotide depletion and PARP1 trapping as an important mechanism of radiosensitization in KRAS-mutant tumors and supports further development of DNA replication as a therapeutic target.<i></i>.
|
29133592 |
2018 |
|
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
The results demonstrated that WEE1 mRNA expression was significantly increased in CRC tissues and that this upregulation correlated significantly with hepatic metastasis, distant metastasis and high tumor node metastasis (TNM) stage of CRC.
|
28599436 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53), WM45.1(MUTp53) and LOX(WTp53), further support our hypothesis of a tumor promoting role of Wee1 in melanomas.
|
22719872 |
2012 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
We show that MK-1775, a potent and selective ATP-competitive inhibitor of WEE1, is cytotoxic across a broad panel of tumor cell lines and induces DNA double-strand breaks.
|
23699655 |
2013 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Taken together with other recently published reports, our results add another level of evidence that the efficacy of WEE1 inhibition is influenced by the DNA repair status of a cell and may also be dependent on the tumor type and model evaluated.
|
27616351 |
2016 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Murine autochthonous and human transplant models were used to test the therapeutic efficacy and pharmacodynamic effects of dual treatment.<b>Results:</b> We demonstrate that combined inhibition of mTOR and WEE1 induced potent synergistic cytotoxic effects selectively in <i>KRAS</i>-mutant NSCLC cell lines, delayed human tumor xenograft growth and caused tumor regression in a murine lung adenocarcinoma model.
|
28821559 |
2017 |
|
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Following our development of circulating tumor cell patient-derived explants (CDX) as models that faithfully mirror patient disease, here we exploit CDX to examine new therapeutic options for SCLC.<b>Experimental Design:</b> We investigated the efficacy of the PARP inhibitor olaparib alone or in combination with the WEE1 kinase inhibitor AZD1775 in 10 phenotypically distinct SCLC CDX <i>in vivo</i> and/or <i>ex vivo</i> These CDX represent chemosensitive and chemorefractory disease including the first reported paired CDX generated longitudinally before treatment and upon disease progression.<b>Results:</b> There was a heterogeneous depth and duration of response to olaparib/AZD1775 that diminished when tested at disease progression.
|
29941481 |
2018 |