|
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 |
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 |
AlteredExpression
|
group |
BEFREE |
Upregulated WEE1 expression was observed in GIST tissues and correlated with tumor size, mitotic count, and risk grade.
|
31197522 |
2020 |