|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Thus, the ATR inhibitor BAY 1895344 may provide new therapeutic options for the treatment of cancers with certain DDR deficiencies in monotherapy and in combination with DNA damage-inducing or DNA repair-compromising cancer therapies by improving their efficacy.
|
31582533 |
2020 |
|
Malignant Neoplasms
|
0.400 |
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
|
0.400 |
Biomarker
|
group |
BEFREE |
In this study, we investigated the role of ATR in cell-cycle arrest by withaferin A (WA), a cancer preventative steroidal lactone derived from Withania somnifera plant abundant in India and surrounding countries.
|
31441116 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
However, whether ATR functions in a similar manner in non-replicating cells has not been examined and is important considering the fact that most cells in the body, including cancer stem cells in solid tumors, normally reside in either a quiescent or differentiated non-replicating state.
|
31557599 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
In this study, we found that forced mitotic entry upon ATR inhibition potentiates cytotoxic effects of PARP inhibition using olaparib in BRCA2-depleted and Brca2 knockout cancer cell line models.
|
31529615 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Here, we investigated whether RS induced by the nucleotide analog fludarabine and specific kinase inhibitors [e.g. targeting checkpoint kinase 1 (Chk1) or ataxia telangiectasia and Rad3-related (ATR)] led to apoptosis or senescence in four cancer cell lines differing in TP53 mutation status and expression of lamin A/C (LA/C).
|
30982228 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Moreover, the combination with PARP or ATR inhibitors has synergistic lethality in some cancers.
|
31299316 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is sensitive to the hallmarks of cancer, as it analyses the full range of macromolecular classes.
|
31612875 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Ataxia telangiectasia and Rad3-related inhibitors and cancer therapy: where we stand.
|
31018854 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Limited data have been published about the effect of these drugs on the tumor microenvironment.<b>Experimental Design:</b> We used an immunocompetent mouse model of HPV-driven malignancies to investigate the ATR inhibitor AZD6738 in combination with fractionated radiation (RT).
|
30770349 |
2019 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
The ataxia telangiectasia and Rad3-related (ATR) protein kinase promotes cancer cell survival by signaling stalled replication forks generated by replication stress, a common feature of many cancers including acute myeloid leukemia (AML).
|
29789314 |
2018 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Interestingly, the cancer promoting effects of ATR-deficient cells were repressed by ectopic expression of the ATR effector p53.
|
30410668 |
2018 |
|
Malignant Neoplasms
|
0.400 |
GeneticVariation
|
group |
BEFREE |
Mutations in p53, critical for G1 checkpoint control, are common in cancer and predicted to confer vulnerability to ATR inhibitors.
|
30127241 |
2018 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Targeting RS by combined inhibition of ATR and PARP (CAiPi) provided GSC-specific cytotoxicity and complete abrogation of GSC radiation resistance <i>in vitro</i> These data identify RS as a cancer stem cell-specific target with significant clinical potential.<b>Significance:</b> These findings shed new light on cancer stem cell biology and reveal novel therapeutics with the potential to improve clinical outcomes by overcoming inherent radioresistance in GBM.<i>Cancer Res; 78(17); 5060-71.©2018 AACR</i>.
|
29976574 |
2018 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Therefore, ATR has become an attractive therapeutic target in cancer therapy.
|
30094103 |
2018 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
These results reveal mechanistic differences between ATR inhibition and ATR loss, with implications for ATR signaling and cancer therapy.
|
30559436 |
2018 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Accordingly, decreased p38α signaling results in impaired ATR activation and homologous recombination repair, with concomitant increases in replication stress, DNA damage, and chromosome instability, leading to cancer cell death and tumor regression.
|
29805078 |
2018 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
We conclude that an improved understanding of both similarities and differences in the cellular mechanisms among the cancer, normal and mESCs is crucial to develop a potential clinical relevance, and ATR-FITR can be successfully used as a novel approach to gain new insights into the stem cell and cancer research.
|
29497718 |
2018 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
We show here that the ATR kinase inhibitor AZD6738 combines with conformal radiation therapy to attenuate radiation-induced CD8+ T cell exhaustion and potentiate CD8+ T cell activity in mouse models of Kras-mutant cancer.
|
29952768 |
2018 |
|
Malignant Neoplasms
|
0.400 |
GeneticVariation
|
group |
BEFREE |
Taken together, our results demonstrate that ATR may represent a novel therapeutic target in patients with MDS carrying the U2AF1(S34F) mutation and potentially other malignancies harboring spliceosome mutations.<b>Significance:</b> This study provides preclinical evidence that patients with MDS or other myeloid malignancies driven by spliceosome mutations may benefit from ATR inhibition to exploit the R loop-associated vulnerability induced by perturbations in splicing.<i>Cancer Res; 78(18); 5363-74.©2018 AACR</i>.
|
30054334 |
2018 |
|
Malignant Neoplasms
|
0.400 |
GeneticVariation
|
group |
BEFREE |
Taken together, our results provide a functional rationale to profile human tumors for disabling <i>ATM</i> mutations, particularly given their impact on PARP1 and ATR inhibitors.<i>Cancer Res; 77(11); 3040-56.©2017 AACR</i>.
|
28363999 |
2017 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
As such, inhibition of ATR can amplify the effects of chemo- and radiation-therapy, and several ATR inhibitors (ATRi) have already undergone clinical testing in cancer.
|
28157626 |
2017 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
In particular, the clinical kinase inhibitors for the treatment of cancer, roniciclib (pan-CDK inhibitor), BAY 1143572 (P-TEFb inhibitor), and AZD 6738 (ATR inhibitor), have recently drawn considerable attention.
|
28221724 |
2017 |
|
Malignant Neoplasms
|
0.400 |
Biomarker
|
group |
BEFREE |
Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer.
|
29209046 |
2017 |
|
Malignant Neoplasms
|
0.400 |
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 |