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293 results for “PARP”
Dataset related to article "Distribution of pamiparib, a novel inhibitor of poly(ADP-ribose)-polymerase (PARP), in tumor tissue analyzed by multimodal imaging"
<p>This record contains data related to article "Distribution of pamiparib, a novel inhibitor of poly(ADP-ribose)-polymerase (PARP), in tumor tissue analyzed by multimodal imaging"</p> <p><span>Pamiparib is a potent and selective oral PARP1/2 inhibitor (PARPi). Pamiparib has good bioavailability and showed greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib. It is not affected by ATP-binding cassette transporters. Consequently, pamiparib may be useful in overcoming drug resistance caused by poor drug distribution in tumor due to overexpression of these efflux pump [1]. Mass spectrometry imaging (MSI) is a powerful technology that allows to study drugs distribution in tissues while maintaining spatial information [2]. Here, MSI was applied to visualize pamiparib in tumor in combination with spatial metabolomics and lipidomics, LC-MS/MS analysis, immunofluorescence analysis, and histological staining to gain a comprehensive understanding of how pamiparib is distributed. The results show that pamiparib was evenly distributed in ovarian tumor models, including those that overexpress P-glycoprotein (P-gp). In contrast, olaparib was not detected by MSI in any of the analyzed tumors, despite the comparable sensitivity of the analytical method. This difference in tumor distribution was confirmed by LC-MS/MS analysis. </span></p>
REVITALIZE: A Telehealth Intervention for Women With Advanced Ovarian Cancer and PARP Inhibitor-Related Fatigue
ClinicalTrials.gov study NCT04525183. IPD Sharing: YES. Countries: 1. Publications: 1.
ROS-Specific Huntingtin Interactions: Chromatin Retention of Huntingtin in PARP KO Cells
<p>Huntingtin chromatin retention in response to oxidative stress in wild type, PARP1 knockout, PARP2 knockout, and PARP1/PARP2 knockout RPE1 cells.</p>
BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistant BRCA-mutant ovarian cancer
<p>PARP inhibitors (PARPis) have changed the treatment paradigm in BRCA-mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for novel therapeutic strategies. Using high-throughput drug screens, we identified ATR/CHK1 pathway inhibitors as cytotoxic, and further validated monotherapy activity of the CHK1 inhibitor (CHK1i), prexasertib, in PARPi-resistant BRCA-mutant HGSC cells and animal models. As a proof-of-concept trial, we conducted a phase II study of prexasertib in BRCA-mutant HGSC patients. The treatment was well-tolerated but yielded an objective response rate of 6% (1/17; 1 PR) in patients with prior PARPi treatment. Exploratory biomarker analyses revealed that replication stress and fork stabilization were associated with clinical benefit to CHK1i. In particular, overexpression of BLM, and CCNE1 overexpression or copy number gain/amplification were seen in patients deriving durable benefit from CHK1i. Our findings suggest replication fork–related biomarkers should be further evaluated for CHK1i sensitivity in HGSC.</p>
Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer
ClinicalTrials.gov study NCT00494234. IPD Sharing: YES. Countries: 8. Publications: 1.
PARP Inhibition for Triple Negative Breast Cancer (ER-/PR-/HER2-)With BRCA1/2 Mutations
ClinicalTrials.gov study NCT01074970. IPD Sharing: Not stated. Countries: 1. Publications: 0.
BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment
ClinicalTrials.gov study NCT02326844. IPD Sharing: NO. Countries: 1. Publications: 3.
Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors
ClinicalTrials.gov study NCT03330405. IPD Sharing: YES. Countries: 9. Publications: 1.
A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study)
ClinicalTrials.gov study NCT01945775. IPD Sharing: YES. Countries: 16. Publications: 3.
A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors
ClinicalTrials.gov study NCT03343054. IPD Sharing: NO. Countries: 1. Publications: 2.
Pilot Trial of BMN 673, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Deleterious BRCA Mutations
ClinicalTrials.gov study NCT01989546. IPD Sharing: NO. Countries: 1. Publications: 4.
REVITALIZE: RCT to Reduce Fatigue in Adults With Ovarian Cancer on PARP Inhibitors
ClinicalTrials.gov study NCT06710548. IPD Sharing: YES. Countries: 1. Publications: 0.
Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin in People With Refractory Solid Tumors
ClinicalTrials.gov study NCT02723864. IPD Sharing: YES. Countries: 1. Publications: 5.
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer
ClinicalTrials.gov study NCT00494442. IPD Sharing: Not stated. Countries: 5. Publications: 3.
Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer
ClinicalTrials.gov study NCT00628251. IPD Sharing: Not stated. Countries: 9. Publications: 6.
Avelumab and Talazoparib in Untreated Advanced Ovarian Cancer (JAVELIN OVARIAN PARP 100)
ClinicalTrials.gov study NCT03642132. IPD Sharing: YES. Countries: 10. Publications: 1.
BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistant BRCA-mutant ovarian cancer
Open the record for dataset details and reuse information.
Structural dynamics of DNA strand break sensing by PARP-1 at a single-molecule level
<p><span>Single-stranded breaks (SSBs) are the most frequent DNA lesions threatening genomic integrity. A highly kinked DNA structure in complex with human PARP-1 domains led to the proposal that SSB sensing in Eukaryotes relies on dynamics of both the broken DNA double helix and PARP-1's multi-domain organization. Here, we directly probe this fundamental yet poorly understood process at the single-molecule level. Quantitative smFRET and structural ensemble calculations reveal how PARP-1's N-terminal zinc fingers convert DNA SSBs from a largely unperturbed conformation, via an intermediate state into the highly kinked DNA conformation. Our data suggest an induced fit mechanism via a multi-domain assembly cascade that drives SSB sensing and stimulates an interplay with the scaffold protein XRCC1 orchestrating subsequent DNA repair events. Interestingly, a clinically used PARP-1 inhibitor Niraparib shifts the equilibrium towards the unkinked DNA conformation, whereas the inhibitor EB47 stabilizes the kinked state. </span></p>
Study of BMN 673, a PARP Inhibitor, in Patients With Advanced Hematological Malignancies
ClinicalTrials.gov study NCT01399840. IPD Sharing: NO. Countries: 2. Publications: 1.
ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide and/or Irinotecan Patients With Previously Treated, Incurable Ewing Sarcoma
ClinicalTrials.gov study NCT02044120. IPD Sharing: Not stated. Countries: 2. Publications: 1.
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