Ontology highlight
ABSTRACT:
PROVIDER: PRJNA626436 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11568930_1.fastq.gz | Fastqsanger.gz | |||
| SRR11568930_2.fastq.gz | Fastqsanger.gz | |||
| SRR11671530_1.fastq.gz | Fastqsanger.gz | |||
| SRR11671530_2.fastq.gz | Fastqsanger.gz | |||
| SRR11671531_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:Euchromatin methyltransferase1/2 (EHMT1/2) have been correlated with tumorigenesis and therapy resistance through unknown mechanisms of action. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory EHMT and PARP inhibition is effective in treating PARP inhibitor resistant ovarian cancers. Our in vitro studies show that combinatory therapy reactivates transposable elements and increased immunostimulatory dsRNA formation and several immune signaling pathways. Our in vivo studies show that single EHMT and combinatory EHMT and PARP inhibition reduces tumor burden and that this reduction is dependent on CD8 T cells. Together, our results show a direct mechanism by which transposable elements are regulated and how an epigenetic therapy can be used as a fine tune agent to treat cancers with specific genetics.
2023-06-14 | GSE224062 | GEO
Project description:Euchromatin methyltransferase1/2 (EHMT1/2) have been correlated with tumorigenesis and therapy resistance through unknown mechanisms of action. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory EHMT and PARP inhibition is effective in treating PARP inhibitor resistant ovarian cancers. Our in vitro studies show that combinatory therapy reactivates transposable elements and increased immunostimulatory dsRNA formation and several immune signaling pathways. Our in vivo studies show that single EHMT and combinatory EHMT and PARP inhibition reduces tumor burden and that this reduction is dependent on CD8 T cells. Together, our results show a direct mechanism by which transposable elements are regulated and how an epigenetic therapy can be used as a fine tune agent to treat cancers with specific genetics.
2024-12-18 | GSE268078 | GEO
Project description:Euchromatin methyltransferase1/2 (EHMT1/2) have been correlated with tumorigenesis and therapy resistance through unknown mechanisms of action. Using a combination of experimental and bioinformatic analyses in several PARP inhibitor resistant ovarian cancer models, we demonstrate that combinatory EHMT and PARP inhibition is effective in treating PARP inhibitor resistant ovarian cancers. Our in vitro studies show that combinatory therapy reactivates transposable elements and increased immunostimulatory dsRNA formation and several immune signaling pathways. Our in vivo studies show that single EHMT and combinatory EHMT and PARP inhibition reduces tumor burden and that this reduction is dependent on CD8 T cells. Together, our results show a direct mechanism by which transposable elements are regulated and how an epigenetic therapy can be used as a fine tune agent to treat cancers with specific genetics.
2023-06-14 | GSE225338 | GEO
Project description:Alteration of the gene encoding BRCA2, a protein involved in homologous recombination (HR), by missense or nonsense mutations results in sensitivity of a subset of breast and ovarian cancers to platinating agents and poly(ADP-ribose) polymerase (PARP) inhibitors. Conversely, resistance to these agents is often accompanied by secondary BRCA2 mutations that restore a functional protein. Here we characterized clones derived from the BRCA2-mutant ovarian cancer line PEO1 by selection with the PARP inhibitor veliparib. Colony forming assays demonstrated cross-resistance of the resulting clones to multiple PARP inhibitors and cisplatin. Despite the continued presence of a 4965C>A (p.Y1655X) BRCA2 nonsense mutation, HR was restored in the resistant cells. Immunoprecipitation followed by immunoblotting or mass spectrometry demonstrated expression of low levels of BRCA2 protein, including peptides distal to the premature termination codon. Reporter assays demonstrated readthrough selective for the UAG stop codon in the veliparib-resistant clones but not parental PEO1 cells; and mass spectrometry revealed insertion of tyrosine rather than termination in the readthrough product. Mass spectrometry and immunoblotting provided evidence for readthrough of UAGs in additional proteins in the resistant clones. BRCA2 gene interruption 3’ to the stop codon restored sensitivity of the resistant clones to PARP inhibitors and cisplatin, implicating the low level BRCA2 expression in resistance. Accordingly, the present results identify low level readthrough of nonsense codons as a potential mechanism of drug resistance that might need to be considered when assessing the impact of mutations on the biology of cancers.
2025-10-27 | PXD037989 | Pride
Project description:Amplification and expression of the MYC oncogene in tumor cells, including ovarian cancer cells correlates with poor responses to chemotherapy. As MYC is not directly targetable, we have analyzed molecular pathways downstream of MYC to identify potential therapeutic targets. We have discovered that ovarian cancer cells overexpressing glutaminase (GLS), a MYC target and a key enzyme in glutaminolysis, are intrinsically resistant to platinum chemotherapy, and are enriched in the intracellular antioxidant glutathione. Deprivation of glutamine by glutamine-withdrawal, GLS knockdown, or exposure to the GLS inhibitor CB-839 resulted in robust induction of reactive oxygen species in high GLS-expressing but not low GLS-expressing ovarian cancer cells. Treatment with CB-839 rendered GLShigh 10 cells vulnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tumor-bearing mice. Our findings suggest that applying a combined therapy of GLS inhibitor and PARP inhibitor could effectively treat chemoresistant ovarian cancers, especially those with high GLS expression.
2020-07-23 | GSE154941 | GEO
Project description:Ovarian high-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer with limited therapeutic options. In recent years, PARP inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Therapies disrupting the spliceosome alter cancer transcriptomes and have shown potential to improve PARP inhibitor response. Indisulam (E7070) has been identified as a molecular glue that brings splicing factor RBM39 and DCAF15 E3 ubiquitin ligase in close proximity. Exposure to indisulam induces RBM39 proteasomal degradation through DCAF15-mediated polyubiquitination and subsequent RNA splicing defects. In this study, we demonstrate that loss of RBM39 induces splicing errors in DNA damage repair genes in ovarian cancer, leading to increased sensitivity to PARP inhibitors such as olaparib. Indisulam synergized with olaparib in multiple in vitro models of ovarian cancer regardless of PARP inhibitor sensitivity and improved olaparib response in mice bearing PARP inhibitor-resistant tumors. DCAF15 expression, but not BRCA1/2 mutational status, was essential for the synergy between indisulam and olaparib, suggesting that the combination therapy may benefit patients irrespective of their BRCA1/2 status. These findings demonstrate that combining RBM39 degraders and PARP inhibitors is a promising therapeutic approach to improving PARP inhibitor response in ovarian HGSC
2023-01-22 | GSE223011 | GEO
Project description:Despite numerous therapeutic advances over the years, ovarian cancer, especially high grade serous ovarian carcinoma remains the deadliest gynecological malignancy. Although PARP inhibition has been shown to be an effective (maintenance) therapy for homologous recombination repair deficient or BRCA1 mutated ovarian cancer, there may be further potential for combination therapy with other drugs such as immune checkpoint inhibitors. BRCA1 mutation as well as PARP inhibitor (Olaparib) treatment influenced the activation of immune response pathways such as cGAS-STING signaling and Interferon-alpha response in ovarian cancer cell lines. Bioinformatics functional analyses uncovered further immune related cellular responses and signaling pathways such as JAK-STAT signaling.
2023-08-01 | GSE237361 | GEO
Project description:PARP inhibitors (PARPi) have demonstrated efficacy in treating human cancers with BRCA1 or BRCA2 gene mutations, which are present in only a small portion of breast, ovarian, prostate, and pancreatic cancers. In this study, we discovered that OFD1 is highly expressed in pancreatic cancer and is associated with a poor prognosis. Through screening an FDA-approved drug library, we found that OFD1 knockdown synergizes most effectively with PARPi for the treatment of pancreatic cancer cells. To explore the mechanism of OFD1 knockdown and PARP inhibitor-induced synthetic lethality, we knocked down OFD1 in three pancreatic cancer cell lines and performed RNA sequencing analysis of the whole genome to investigate the mechanisms underlying OFD1 inhibition and PARP inhibitor-induced synthetic lethality. In summary, our research will provide insights into the role of OFD1 in pancreatic cancer by revealing changes in the whole-genome expression profile and the underlying mechanisms.
2025-06-08 | GSE282746 | GEO
Project description:Non-small cell lung cancer (NSCLC) is often treated with cisplatin (CDDP). Here, we report that two distinct poly(ADP-ribose) polymerase (PARP) inhibitors exhibited a hyperadditive combination effect with CDDP to kill NSCLC cells. A majority of CDDP-resistant cell lines and clones exhibited constitutively increased PARP expression and enzymatic activity. Cells with hyperactivated PARP initiated a DNA damage response and the intrinsic pathway of apoptosis in response to pharmacological PARP inhibition or PARP1-targeting siRNAs. Transcriptome analysis depicted an unsupervised hierarchical clustering of NSCLC cells and CDDP resistant counterparts regarding to their response to PARP inhibitors. PARP-overexpressing tumors displayed elevated levels of intracellular poly(ADP-ribose) (PAR), which predicted the response to PARP inhibitors in vitro and in vivo more accurately than PARP expression itself. Thus, CDDP-resistant cancer cells develop a dependency to PARP, becoming susceptible to PARP inhibitor-induced apoptosis.
2013-10-31 | E-MTAB-1353 | biostudies-arrayexpress