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 |
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 |
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 |
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 |
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 |
Sequential inhibition of PARP and WEE1 limits tumor growth and reduces toxicity in multiple cancers.
|
31227515 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Oncogene-induced replication stress serves as a tumour specific vulnerability and rationale for the clinical development of inhibitors targeting the DNA damage response (DDR) kinases (CHK1, ATR, ATM and WEE1).
|
31500184 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
HER2/CCNE1-amplified PDCs were considerably resistant to an HER2 inhibitor, while combinational treatment consisting of an HER2 inhibitor with anti-WEE1 compound substantially suppressed tumor cellular growth.
|
31850215 |
2019 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma.
|
30323762 |
2018 |
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 |
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 |
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 |
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 |
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 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Wee1 inhibition can suppress tumor proliferation and sensitize p53 mutant colonic cancer cells to the anticancer effect of irinotecan.
|
29257266 |
2018 |
Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
<b>Purpose:</b> The WEE1 tyrosine kinase regulates G<sub>2</sub>-M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy.
|
29535125 |
2018 |
Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Tumor cell sensitivity to cultured murine KIL and human high affinity NK (haNK) cells in the presence or absence of AZD1775, a small molecule inhibitor of WEE1 kinase, was assessed via real time impedance analysis.
|
29925431 |
2018 |
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 |
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 |
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 |
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 |
AZD1775, an inhibitor against the critical G<sub>2</sub>-M checkpoint protein WEE1, is currently in clinical trials across a number of tumor types.
|
28652249 |
2017 |
Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Significantly, the WEE1 inhibitor AZD1775 not only abrogated the suppressive H2B Y37-phosphorylation and upregulated <i>IDH2</i> mRNA levels but also effectively reversed the 'loss of 5-hmC' phenotype in melanomas, GBMs and prostate cancer cells, as well as melanoma xenograft tumors.
|
29290954 |
2017 |