Global ETD Search
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Showing 1 to 20 of 30 for “"PARP inhibitors"”.
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Δεδομένα φαρμακοεπαγρύπνησης των PARP inhibitors στον καρκίνο ωοθηκών και μαστού / Pharmacovigilance data of PARP inhibitors in ovarian and breast cancer
… η τοξικότητα των φαρμάκων είναι αρκετά υψηλή. Οι PARP αναστολείς (Poly ADP-Ribose Polymerase inhibitors) ανήκουν σε μία οικογένεια ενζύμων που λόγω της συνθετικής θνησιμότητας που προσφέρουν χρησιμοποιούνται στην ογκολογία ως στοχευμένες αντικαρκινικές θεραπείες. Στην παρούσα διπλωματική, …
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Development of Rational Combination Therapy With Parp Inhibitors and Kinase Inhibitors In Tnbc
<p>Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. …
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Role of C-Met and Egfr In Acquired Resistance to Parp Inhibitors In Triple-Negative Breast Cancer
… are limited. The Poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and talazoparib, were recently approved for metastatic breast cancer (including triple-negative breast cancer) in patients with a germline <em>BRCA1/2</em> mutation. Despite impressive response rates of ~60%, the …
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Developing 1,2,3,4-tetrahydro-5H-aryl[1,4]diazepin-5-ones and Related Scaffolds as Poly-(ADP-ribosyl) Polymerase (PARP) Inhibitors and Exploring Their Targeted Polypharmacology with Kinases
Poly-(ADP-ribsoyl) Polymerases (PARPs) are a superfamily of enzymes comprised of 17 known isoforms. PARP inhibitors (PARPi) have shown success in clinical trials for the treatment of homologous recombination-deficient cancers. Though proven effective initially, tumors treated with PARPi eventually …
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Tracking Treatment Response and Resistance to Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer.
<p>polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous …
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Improving the Efficacy and Expanding the Application of NQO1-Bioactivated Therapeutics
… stress of NAD+ and ATP depletion induced by PARP1 hyperactivation secondary to ß-lap treatment. This resulted in synergistic cancer cell death at normally sublethal doses of both ß-lap and NAMPT inhibitors, occurring through the same NAD+-Keresis mechanism as with ß-lap alone. On the other …
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Rational identification of a dual inhibitor of PARP-1 and ATM kinase
… to cancer cells, which can be exploited by DDR inhibitors. PARP inhibitors are used to exploit the synthetic lethality between pharmacological inhibition of PARP (poly-ADP ribose polymerase) and BRCA (breast cancer gene) defects leading to successful patient treatment in ovarian, breast and …
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Identification of the Phosphatase NUDT5 as a Target for the Treatment of Triple Negative Breast Cancer
… patients remain as conventional chemotherapy and PARP inhibitors (only applicable for a subset of BRCA-mutated TNBC patients). Consequently, our focus has been on the exploration of innovative targeted therapies for TNBC. This study investigated the novel phosphatase, NUDT5, as a potential …
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The effect of distinct BRCA1 splice forms on drug sensitivity in breast- and ovarian cancer cell lines
… development, particularly in breast and ovaries. PARP inhibitors are a promising treatment option for carriers of BRCA1/2 mutations diagnosed with these tumor types. Pathogenic spliceogenic variants have been found in BRCA1 that change the expression of BRCA1 transcripts, in which the expression …
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Enzymatic synthesis of defined-length poly(ADP-ribose) and the investigation of cell-permeable poly(ADP-ribose) glycohydrolase inhibitors
… this end, various Poly(ADP-ribose) Polymerase (PARP) inhibitors have been developed to induce sensitivity to genotoxic stress in BRCA-mutated cancer cells, and Poly(ADP-ribose) Glycohydrolase (PARG) inhibition is investigated as an alternate pathway to PARP inhibition in genotoxic chemotherapy. …
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Studies of PARP-1 activation and inhibition using NMR spectroscopy
Poly(ADP-ribose)polymerase 1 (PARP-1) is a highly abundant multi-domain chromatin-associated enzyme found in all higher eukaryotic cell nuclei. It is the founding member of the PARP family of enzymes that modify themselves and other proteins by adding negatively charged poly(ADP-ribose) chains …
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SOX2 is Associated with Changes in DNA Damage Repair and Cell Cycle Gene Expression and Regulates E2F1
… to determine if Poly (ADP-Ribose) Polymerase (PARP) inhibitors are an appropriate treatment option. One potential biomarker my lab has identified is SOX2. The expression of SOX2 was linked to an increased Gleason score at diagnosis and decreased time to metastasis after biochemical recurrence. …
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Spectrum and Incidence of Primary and Therapy-Related Hematologic Malignancies In Individuals With Brca1 and Brca2 Pathogenic Variants
… (adenosine diphosphate-ribose)-ADP polymerase (PARP) inhibitors. Preliminary evidence suggests that germline <em>BRCA1</em> and <em>BRCA2</em> pathogenic and likely pathogenic (P/LP) variants may increase susceptibility to t-MNs due to the genes’ established role in DNA damage response. There is …
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Parp Inhibitor Upregulates Pd-L1 Expression and Enhances Cancer-Associated Immunosuppression
… patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, …
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Selection of a Non-Phosphorylated Peptide Inhibitor of BRCA1’s (BRCT)2 Domain
… cells treated with radiation as well as PARP inhibitors and other chemotherapeutics demonstrate a greater sensitivity than cells with wild type BRCA1. Inhibitors of BRCA1 would take advantage of this synthetic lethality and represent a significant advance in cancer treatment as well as an …
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CRISPR/Cas9 screenings and in silico investigations nominate low-frequency alterations in DNA repair genes as biomarkers for castration-resistant prostate cancers.
PARP inhibitors (PARPi) have received regulatory approval for the treatment of multiple tumor types, including prostate cancer (PCa), and are associated with therapeutic response in metastatic castration-resistant prostate cancer (mCRPC) patients characterized by defects in homologous recombination …
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PARP inhibition in combination with radiation therapy for the treatment of feline oral squamous cell carcinoma
… are needed. Poly (ADP-ribose) polymerase (PARP) is a key molecule involved in single stranded DNA break repair. PARP inhibitors (PARPi) are predicted to amplify RT-induced lethal DNA damage, and combinatorial strategies with PARPi and RT are being investigated for treating human solid …
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Combination Chemotherapy and In vivo Modeling of BRCA-deficient, High-grade Serous Ovarian Cancer
… platinum sensitivity. Novel therapeutics such as PARP inhibitors have also been developed by exploiting the synthetic lethal phenotype of BRCA inactivation and PARP inhibition. However over 80% of patients still relapse with resistant disease. Therefore, strategies for more effective treatment are …
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Targeting Autophagy to Improve Efficacy of Cdk4/6 Inhibition In Breast Cancer
… FDA approval (palbociclib, ribociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, three major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of reliable biomarkers to identify responsive …
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Poly (Adp) Ribose Polymerase Inhibitors For The Treatment of Malignant Peripheral Nerve Sheath Tumor
… MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with <em>BRCA1/2</em> (breast cancer, early onset 1/2)<em> </em>mutations. Further …
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