Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer

ABSTRACT: CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer

PROVIDER: PRJNA1039833 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26815457_1.fastq.gz	Fastqsanger.gz
	SRR26815457_2.fastq.gz	Fastqsanger.gz
	SRR26815458_1.fastq.gz	Fastqsanger.gz
	SRR26815458_2.fastq.gz	Fastqsanger.gz
	SRR26815459_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer

Project description:PARP inhibitors have demonstrated remarkable clinical efficacy in treating ovarian cancer (OV) patients with BRCA1/2 mutations. However, drug resistance inevitably limits their clinical applications and there is an urgent need for improved therapeutic strategies to enhance the clinical utility of PARP inhibitors, such as Olaparib. Here, we present compelling evidence that PARP inhibitor sensitivity is associated with cell cycle dysfunction, independent of homologous recombination deficiency (HRD) /BRCA status. Through high-throughput drug screening with a cell cycle kinase inhibitor library, we identified XL413, a potent CDC7 inhibitor, which can synergistically enhance the anti-cancer efficacy of Olaparib. Mechanistically, we demonstrate that the combined administration of XL413 and Olaparib induced considerable DNA damage and DNA replication stress, leading to increased sensitivity to Olaparib. Additionally, a robust type-I interferon response was triggered through the induction of the cGAS/STING signaling pathway. Using a murine syngeneic tumor model, we further demonstrate that the combination treatment enhanced antitumor immunity, resulting in tumor regression. Collectively, this study presents a novel treatment strategy for patients with advanced OV by combining CDC7 and PARP inhibitiors, offering a promising therapeutic approach forpatients whith limited response to PARP inhibitors.

2024-12-18 | GSE247622 | GEO

PARP inhibition elicits STING-dependent antitumor immune responses in Brca1-deficient ovarian cancer

Project description:To examine the immune responses that occur in Brca1-deficent tumors upon olaparib treatment, we performed gene expression analysis of a panel of 4604 cancer and immune-related genes in tumor tissues harvested from Brca1-deficient ovarian tumor-bearing mice after treatment with olaparib or vehicle. Transcriptome analysis showed that the expression of genes associated with immune response, T-cell activation and interferon-gamma(IFNgamma) response were markedly upregulated in tumors treated with olaparib as compared to vehicle. Our data reveal the antitumor immune response of PARP inhibition and demonstrate that it contributes to therapeutic efficacy of PARP inhibition in Brca1-deficient tumors.

2019-02-13 | GSE120500 | GEO

The role of CDC7 in Melanoma cancer growth and progression

Project description:Disruptor of Cell Division Cycle 7 (CDC7) expression is elevated in many cancer types including melanoma. Therefore, we analyzed the role of CDC7 in melanoma. Pharmacological inhibition of CDC7 expression in Melanoma cancer cell lines resulted in decreased proliferation, and increased cell death.

2022-08-10 | GSE158621 | GEO

Localization of Cdc7 Protein Kinase During DNA Replication in Saccharomyces cerevisiae

Project description:Cdc7 kinase is known to initiate DNA replication, but it is unknown where Cdc7 is found within the genome. We modified the Calling Cards method that uses the Ty5 retrotransposon to investigate Cdc7 binding in the genome. The Ty5 retrotransposon is inserted into the genome by DNA transcription factors or replication factors binding within the genome. We find that Cdc7 inserts Ty5 transposons throughout chromosomes and furthermore creates more Ty5 insertions into regions of DNA that are known to replicate early. Cdc7 does not solely integrate Ty5 at origins or replication, but rather throughout the genome.

2017-09-18 | GSE103943 | GEO

DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.

Project description:In eukaryotes, CDC7 kinase is crucial for DNA replication initiation and has been involved in fork processing and replication stress response. Human CDC7 requires the binding of either one of two regulatory subunits, DBF4 and DRF1, for its activity. However, it is unclear whether the two regulatory subunits target CDC7 to a specific set of substrates, thus having different biological functions, or if they act redundantly. Using genome editing technology, we generated an isogenic set of cell lines deficient in either one of the two CDC7-activating subunits: these cells are viable but present signs of genomic instability, indicating that both DBF4 and DRF1 can independently support CDC7 for bulk DNA replication. Nonetheless, DBF4-deficient cells show altered replication efficiency, including partial deficiency in MCM helicase phosphorylation and alterations in the replication timing of discrete genomic regions. Notably, we find that CDC7 function at replication forks is entirely dependent on DBF4 and not DRF1. Thus, DBF4 is the primary regulator of CDC7 activity, likely mediating most of its functions in unperturbed DNA replication and during replication fork processing upon replication interference.

2024-03-28 | GSE248981 | GEO

PARP inhibition elicits STING-dependent antitumor immune responses in Brca1-deficient ovarian cancer

Project description:PARP inhibition elicits STING-dependent antitumor immune responses in Brca1-deficient ovarian cancer

| PRJNA493223 | ENA

Hippo signaling-controlled MHC-I antigen processing and presentation pathway potentiates antitumor immunity

Project description:Hippo signaling-controlled MHC-I antigen processing and presentation pathway potentiates antitumor immunity

| PRJNA1063716 | ENA

Combinatorial treatment with PARP and MAPK inhibitors to overcome phenotype switch-driven drug resistance in advanced melanoma

Project description:The prognosis for most patients with advanced malignant melanoma is traditionally very poor, as the disease is either intrinsically resistant or rapidly acquires resistance to targeted therapy treatments. Here, using a drug screen targeting chromatin regulators in patient-derived 3D melanoma cell cultures, we discovered that PARP inhibitors are capable of restoring MAPKi sensitivity. This synergy was found to be independent of DNA damage repair pathways and was effective both in vitro and in vivo in patients-derived xenografts. Strikingly, through integrated transcriptomic, proteomic and epigenomic analysis, we discovered that PARPi induces lysosomal autophagy which was accompanied by enhanced mitochondrial lipid metabolism that, ultimately, increased antigen presentation and T-cell cytotoxicity. Moreover, we also found that PARP inhibitors regulated EMT-like phenotype switching by dampening the mesenchymal phenotype via transcriptomic and epigenetic rearrangements. This, in turn, redirected melanoma cells towards a proliferative and, thus, MAPKi-sensitive state. Our study provides a scientific rational for treating patients with PARPi in combination with MAPKi to annihilate acquired therapy resistance

2023-07-01 | GSE221233 | GEO

PARP inhibition

Project description:PARP inhibition and the effect on Arabidopsis thaliana high light tolerance

2012-05-01 | E-MTAB-896 | biostudies-arrayexpress

CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

Project description:Neuroendocrine (NE) transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor prognosis. Upregulation of the cell cycle kinase CDC7 occurred in tumors undergoing NE transformation, after TP53/RB1 co-inactivation, leading to induced sensitivity to the CDC7 inhibitor simurosertib. CDC7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of MYC, implicated in stemness and histological transformation. Ectopic overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy, even in the presence of simurosertib. CDC7 inhibition also markedly extended response to standard cytotoxics in lung and prostate small cell carcinoma models. These results nominate CDC7 inhibition as a strategy to constrain lineage plasticity and to effectively treat NE tumors. As simurosertib clinical efficacy trials are ongoing, this concept could be readily translated for patients at risk.

2024-05-12 | GSE265887 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data