keyword
https://read.qxmd.com/read/38340425/overexpression-of-abcc1-and-abcg2-confers-resistance-to-talazoparib-a-poly-adp-ribose-polymerase-inhibitor
#1
JOURNAL ARTICLE
Qiu-Xu Teng, Zi-Ning Lei, Jing-Quan Wang, Yuqi Yang, Zhuo-Xun Wu, Nikita Dilip Acharekar, Wei Zhang, Sabesan Yoganathan, Yihang Pan, John Wurpel, Zhe-Sheng Chen, Shuo Fang
AIMS: The overexpression of ABC transporters on cancer cell membranes is one of the most common causes of multidrug resistance (MDR). This study investigates the impact of ABCC1 and ABCG2 on the resistance to talazoparib (BMN-673), a potent poly (ADP-ribose) polymerase (PARP) inhibitor, in ovarian cancer treatment. METHODS: The cell viability test was used to indicate the effect of talazoparib in different cell lines. Computational molecular docking analysis was conducted to simulate the interaction between talazoparib and ABCC1 or ABCG2...
November 29, 2023: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/38010394/pharmacodynamic-effects-of-the-parp-inhibitor-talazoparib-mdv3800-bmn-673-in-patients-with-brca-mutated-advanced-solid-tumors
#2
JOURNAL ARTICLE
Arjun Mittra, Geraldine H O' Sullivan Coyne, Jennifer Zlott, Shivaani Kummar, Robert Meehan, Lawrence Rubinstein, Lamin Juwara, Deborah Wilsker, Jiuping Ji, Brandon Miller, Tony Navas, Katherine V Ferry-Galow, Andrea Regier Voth, Ting-Chia Chang, Shahanawaz Jiwani, Ralph E Parchment, James H Doroshow, Alice P Chen
PURPOSE: Talazoparib is an inhibitor of the poly (ADP-ribose) polymerase (PARP) family of enzymes and is FDA-approved for patients with (suspected) deleterious germline BRCA1/2-mutated, HER2‑negative, locally advanced or metastatic breast cancer. Because knowledge of the pharmacodynamic (PD) effects of talazoparib in patients has been limited to studies of PARP enzymatic activity (PARylation) in peripheral blood mononuclear cells, we developed a study to assess tumoral PD response to talazoparib treatment (NCT01989546)...
November 27, 2023: Cancer Chemotherapy and Pharmacology
https://read.qxmd.com/read/37910601/intrathecal-delivery-of-nanoparticle-parp-inhibitor-to-the-cerebrospinal-fluid-for-the-treatment-of-metastatic-medulloblastoma
#3
JOURNAL ARTICLE
Minsoo Khang, Ju Hyun Lee, Teresa Lee, Hee-Won Suh, Supum Lee, Alessandra Cavaliere, Amy Rushing, Luiz H Geraldo, Erika Belitzky, Samantha Rossano, Henk M de Feyter, Kwangsoo Shin, Anita Huttner, Martine F Roussel, Jean-Leon Thomas, Richard E Carson, Bernadette Marquez-Nostra, Ranjit S Bindra, W Mark Saltzman
The morbidity associated with pediatric medulloblastoma, in particular in patients who develop leptomeningeal metastases, remains high in the absence of effective therapies. Administration of substances directly into the cerebrospinal fluid (CSF) is one approach to circumvent the blood-brain barrier and focus delivery of drugs to the site of tumor. However, high rates of CSF turnover prevent adequate drug accumulation and lead to rapid systemic clearance and toxicity. Here, we show that PLA-HPG nanoparticles, made with a single-emulsion, solvent evaporation process, can encapsulate talazoparib, a PARP inhibitor (BMN-673)...
November 2023: Science Translational Medicine
https://read.qxmd.com/read/37763083/class-i-hdac-inhibition-leads-to-a-downregulation-of-fancd2-and-rad51-and-the-eradication-of-glioblastoma-cells
#4
JOURNAL ARTICLE
Małgorzata Drzewiecka, Dominika Jaśniak, Gabriela Barszczewska-Pietraszek, Piotr Czarny, Anna Kobrzycka, Marek Wieczorek, Maciej Radek, Janusz Szemraj, Tomasz Skorski, Tomasz Śliwiński
HDAC inhibitors (HDACi) hold great potential as anticancer therapies due to their ability to regulate the acetylation of both histone and non-histone proteins, which is frequently disrupted in cancer and contributes to the development and advancement of the disease. Additionally, HDACi have been shown to enhance the cytotoxic effects of DNA-damaging agents such as radiation and cisplatin. In this study, we found that histone deacetylase inhibits valproic acid (VPA), synergized with PARP1 inhibitor (PARPi), talazoparib (BMN-673), and alkylating agent, and temozolomide (TMZ) to induce DNA damage and reduce glioblastoma multiforme...
August 27, 2023: Journal of Personalized Medicine
https://read.qxmd.com/read/37695044/setd2-deficiency-confers-sensitivity-to-dual-inhibition-of-dna-methylation-and-parp-in-kidney-cancer
#5
JOURNAL ARTICLE
Xinyi Zhou, Yohei Sekino, Hong-Tao Li, Guanghou Fu, Zhi Yang, Shuqing Zhao, Hemant Gujar, Xiongbing Zu, Daniel J Weisenberger, Inderbir S Gill, Varsha Tulpule, Anishka D'souza, David I Quinn, Bo Han, Gangning Liang
SETD2 deficiency alters the epigenetic landscape by causing depletion of H3K36me3 and plays an important role in diverse forms of cancer, most notably in aggressive and metastatic clear cell renal cell carcinomas (ccRCC). Development of an effective treatment scheme targeting SETD2-compromised cancer is urgently needed. Considering that SETD2 is involved in DNA methylation and DNA repair, a combination treatment approach using DNA hypomethylating agents (HMA) and PARP inhibitors (PARPi) could have strong anti-tumor activity in SETD2-deficient kidney cancer...
September 11, 2023: Cancer Research
https://read.qxmd.com/read/37461649/parp1-inhibition-halts-ebv-lymphoma-progression-by-disrupting-the-ebna2-myc-axis
#6
Giorgia Napoletani, Samantha S Soldan, Toshitha Kannan, Sarah Preston-Alp, Peter Vogel, Davide Maestri, Lisa Beatrice Caruso, Andrew Kossenkov, Asher Sobotka, Paul M Lieberman, Italo Tempera
UNLABELLED: PARP1 has been shown to regulate EBV latency. However, the therapeutic effect of PARP1 inhibitors on EBV+ lymphomagenesis has not yet been explored. Here, we show that PARPi BMN-673 has a potent anti-tumor effect on EBV-driven LCL in a mouse xenograft model. We found that PARP1 inhibition induces a dramatic transcriptional reprogramming of LCLs driven largely by the reduction of the MYC oncogene expression and dysregulation of MYC targets, both in vivo and in vitro . PARP1 inhibition also reduced the expression of viral oncoprotein EBNA2, which we previously demonstrated depends on PARP1 for activation of MYC...
July 7, 2023: bioRxiv
https://read.qxmd.com/read/37372475/histone-deacetylases-hdac-inhibitor-valproic-acid-sensitizes-human-melanoma-cells-to-dacarbazine-and-parp-inhibitor
#7
JOURNAL ARTICLE
Małgorzata Drzewiecka, Anna Gajos-Michniewicz, Grażyna Hoser, Dominika Jaśniak, Gabriela Barszczewska-Pietraszek, Przemysław Sitarek, Piotr Czarny, Janusz Piekarski, Maciej Radek, Małgorzata Czyż, Tomasz Skorski, Tomasz Śliwiński
The inhibition of histone deacetylases (HDACs) holds promise as a potential anti-cancer therapy as histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, the use of a histone deacetylase inhibitor (HDACi) such as the class I HDAC inhibitor-valproic acid (VPA) has been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that the use of VPA in combination with talazoparib (BMN-673-PARP1 inhibitor-PARPi) and/or Dacarbazine (DTIC-alkylating agent) resulted in an increased rate of DNA double strand breaks (DSBs) and reduced survival (while not affecting primary melanocytes) and the proliferation of melanoma cells...
June 20, 2023: Genes
https://read.qxmd.com/read/36612094/targeted-therapy-with-pi3k-parp-and-wee1-inhibitors-and-radiotherapy-in-hpv-positive-and-negative-tonsillar-squamous-cell-carcinoma-cell-lines-reveals-synergy-while-effects-with-apr-246-are-limited
#8
JOURNAL ARTICLE
Karin Byskata, Monika Lukoseviciute, Filippo Tuti, Mark Zupancic, Ourania N Kostopoulou, Stefan Holzhauser, Tina Dalianis
Human papillomavirus positive (HPV+ ) tonsillar and base of tongue cancer (TSCC/BOTSCC) is rising in incidence, but chemoradiotherapy is not curative for all. Therefore, targeted therapy with PI3K (BYL719), PARP (BMN-673), and WEE1 (MK-1775) inhibitors alone or combined was pursued with or without 10 Gy and their effects were analyzed by viability, proliferation, and cytotoxicity assays on the TSCC/BOTSCC cell lines HPV+ UPCI-SCC-154 and HPV- UT-SCC-60A. Effective single drug/10 Gy combinations were validated on additional TSCC lines...
December 23, 2022: Cancers
https://read.qxmd.com/read/35962813/combination-of-talazoparib-and-olaparib-enhanced-the-curcumin-mediated-apoptosis-in-oral-cancer-cells-by-parp-1-trapping
#9
JOURNAL ARTICLE
Subhajit Chatterjee, Ajit Kumar Dhal, Subarno Paul, Saptarshi Sinha, Biswajit Das, Somya Ranjan Dash, Chanakya Nath Kundu
PURPOSE: Inhibition of Poly (ADP-ribose) Polymerases (PARP) results in the blocking of DNA repair cascades that eventually leads to apoptosis and cancer cell death. PARP inhibitors (PARPi) exhibit their actions either by inhibiting PARP-induced PARylation and/or by trapping PARP at the DNA damage site. But, the mechanism of PARPi-mediated induction of cellular toxicity via PARP-trapping is largely unknown. METHODS: The cellular toxicity of PARPi [Talazoparib (BMN) and/or Olaparib (Ola)] was investigated in oral cancer cells and the underlying mechanism was studied by using in vitro, in silico, and in vivo preclinical model systems...
August 13, 2022: Journal of Cancer Research and Clinical Oncology
https://read.qxmd.com/read/35903712/intrinsic-ros-drive-hair-follicle-cycle-progression-by-modulating-dna-damage-and-repair-and-subsequently-hair-follicle-apoptosis-and-macrophage-polarization
#10
JOURNAL ARTICLE
Mingsheng Liu, Xiaomei Liu, Yuan Wang, Yutong Sui, Feilin Liu, Zinan Liu, Fei Zou, Kuiyang Zuo, Ziyu Wang, Wei Sun, Qi Xu, Dan Liu, Jinyu Liu
Hair follicles (HFs) maintain homeostasis through the hair cycles; therefore, disrupting the hair cycle may lead to hair loss. Our previous study showed that apoptosis-inducing factor (AIF) nuclear translocation and poly [ADP-ribose] polymerase 1 (PARP1) upregulation induced apoptosis in mouse hair follicles during the hair cycle transition from anagen to catagen. However, the mechanism underlying this phenomenon remains unclear. In this study, we found that intrinsic ROS levels increased during the hair follicle cycle transition from anagen to catagen, followed by abrupt DNA breaks and activation of homologous recombinant and nonhomologous end joining DNA repair, along with the enhancement of apoptosis...
2022: Oxidative Medicine and Cellular Longevity
https://read.qxmd.com/read/35891353/targeted-therapy-of-hpv-positive-and-negative-tonsillar-squamous-cell-carcinoma-cell-lines-reveals-synergy-between-cdk4-6-pi3k-and-sometimes-fgfr-inhibitors-but-rarely-between-parp-and-wee1-inhibitors
#11
JOURNAL ARTICLE
Ourania N Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
Human papillomavirus positive (HPV+ ) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have a favorable outcome, but upon relapse, survival is poor and new therapeutical options are needed. Recently, we found synergistic effects by combining the food and drug administration approved (FDA) phosphoinositide 3-kinase (PI3K) and fibroblast-growth-factor-receptor (FGFR) inhibitors BYL719 and JNJ-42756493 on TSCC cell lines. Here this approach was extended and Cyclin-Dependent-Kinase-4/6 (CDK4/6) and Poly-ADP-ribose-polymerase (PARP) and WEE1 inhibitors PD-0332991, and MK-1775 respectively were also examined...
June 23, 2022: Viruses
https://read.qxmd.com/read/35396812/a-phase-i-study-of-talazoparib-bmn-673-combined-with-carboplatin-and-paclitaxel-in-patients-with-advanced-solid-tumors-nci9782
#12
JOURNAL ARTICLE
Ticiana A Leal, Marina N Sharifi, Nancy Chan, Robert Wesolowski, Anita A Turk, Justine Y Bruce, Ruth M O'Regan, Jens Eickhoff, Lisa M Barroilhet, Jyoti Malhotra, Janice Mehnert, Eugenia Girda, Elizabeth Wiley, Natalie Schmitz, Shannon Andrews, Glenn Liu, Kari B Wisinski
BACKGROUND: Inhibitors of poly(ADP-ribose) polymerase (PARP) proteins potentiate antitumor activity of platinum chemotherapy. This study sought to determine the safety and tolerability of PARP inhibitor talazoparib with carboplatin and paclitaxel. METHODS: We conducted a phase I study of talazoparib with carboplatin AUC5-6 and paclitaxel 80 mg/m2  days 1, 8, 15 of 21-day cycles in patients with advanced solid tumors. Patients enrolled using a 3 + 3 design in two cohorts with talazoparib for 7 (schedule A) or 3 days (schedule B)...
April 8, 2022: Cancer Medicine
https://read.qxmd.com/read/34998856/parp-inhibitor-bmn-673-induced-apoptosis-by-trapping-parp-1-and-inhibiting-base-excision-repair-via-modulation-of-pol-%C3%AE-in-chromatin-of-breast-cancer-cells
#13
JOURNAL ARTICLE
Chinmayee Sethy, Chanakya Nath Kundu
PARP inhibitors emerged as clinically effective anti-tumor agents in combination with DNA damaging agents but the toxicity of DNA damaging agents and their off-target effects caused serious problems in cancer therapy. They confer cytotoxicity in cancer cells both by catalytic inhibition and trapping of PARP-1 at the DNA damage site. There is a lack of direct evidence to quantitatively determine the trapped PARP-1 in cellular DNA. Here, we have precisely evaluated the mechanism of PARP trapping mediated anti-cancer action of Quinacrine (QC), BMN-673, and their combination (QC + BMN-673) in breast cancer cells...
February 1, 2022: Toxicology and Applied Pharmacology
https://read.qxmd.com/read/33691794/synergistic-effects-of-type-i-prmt-and-parp-inhibitors-against-non-small-cell-lung-cancer-cells
#14
JOURNAL ARTICLE
Claudia Dominici, Nicolas Sgarioto, Zhenbao Yu, Laura Sesma-Sanz, Jean-Yves Masson, Stéphane Richard, Noël J-M Raynal
BACKGROUND: Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related death and represents a major health burden worldwide. Current therapies for NSCLC include chemotherapy, immunotherapy, and targeted molecular agents such as tyrosine kinase inhibitors and epigenetic drugs such as DNA methyltransferase inhibitors. However, survival rates remain low for patients with NSCLC, especially those with metastatic disease. A major cause for therapeutic failure is drug resistance, highlighting the need for novel therapies and combination strategies...
March 10, 2021: Clinical Epigenetics
https://read.qxmd.com/read/31451894/drug-repurposing-studies-of-parp-inhibitors-as-a-new-therapy-for-inherited-retinal-degeneration
#15
JOURNAL ARTICLE
Ayse Sahaboglu, Maria Miranda, Denis Canjuga, Meltem Avci-Adali, Natalia Savytska, Enver Secer, Jessica Abigail Feria-Pliego, Gülru Kayık, Serdar Durdagi
The enzyme poly-ADP-ribose-polymerase (PARP) has important roles for many forms of DNA repair and it also participates in transcription, chromatin remodeling and cell death signaling. Currently, some PARP inhibitors are approved for cancer therapy, by means of canceling DNA repair processes and cell division. Drug repurposing is a new and attractive aspect of therapy development that could offer low-cost and accelerated establishment of new treatment options. Excessive PARP activity is also involved in neurodegenerative diseases including the currently untreatable and blinding retinitis pigmentosa group of inherited retinal photoreceptor degenerations...
June 2020: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/31347614/talazoparib-to-treat-brca-positive-breast-cancer
#16
REVIEW
G Guney Eskiler
Talazoparib tosylate (BMN-673, Talzenna; Pfizer) is an oral poly [ADP-ribose] polymerase (PARP) inhibitor (PARPi) that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of germline BRCA-mutated locally advanced or metastatic breast cancer (BC). In preclinical and clinical studies, talazoparib exerted superior efficacy and offered a significant clinical benefit in advanced or metastatic BC patients harboring germline BRCA mutations compared with other PARPi and standard chemotherapy regimens through the concept of synthetic lethality...
July 2019: Drugs of Today
https://read.qxmd.com/read/31113350/talazoparib-loaded-solid-lipid-nanoparticles-preparation-characterization-and-evaluation-of-the-therapeutic-efficacy-in-vitro
#17
JOURNAL ARTICLE
Gamze Guney Eskiler, Gulsah Cecener, Gokhan Dikmen, Unal Egeli, Berrin Tunca
OBJECTIVE: In the present work, we report for the first time the therapeutic potential of talazoparib (BMN 673)-SLNs for the treatment of BRCA1 deficient Triple Negative Breast Cancer (TNBC). BMN 673-SLNs were produced by hot-homogenization technique and then characterized. METHODS: The cytotoxic and apoptotic effects of BMN 673-SLNs compared with BMN 673 were determined on HCC1937BRCA1-/-, HCC1937-R resistant TNBC and MCF-10A control cell lines. BMN 673- SLNs were found to have reduced particle size (219...
2019: Current Drug Delivery
https://read.qxmd.com/read/30672063/bmn-673-talazoparib-a-potent-parp-inhibitor-for-triple-negative-breast-cancer-with-different-genetic-profile
#18
JOURNAL ARTICLE
Gamze Guney Eskiler, Gulsah Cecener, Unal Egeli, Berrin Tunca
The objective of the present study was to elucidate the effect of BMN 673 (talozoparib) on BRCA1 mutant (HCC1937) and wild-type (MDA-MB-231) triple negative breast cancer (TNBC). The in vitro cytotoxicity results indicated that BMN 673 had considerable inhibitory effects on HCC1937 and MDA-MB-231 cell lines by inducing apoptosis, multicaspase activity, G2/M arrest, and altering the expression levels of apoptosis-related genes (P < 0.01). Additionally, BMN 673 indicated no toxicity on MCF-10A control cells until a certain concentration and incubation time...
May 2019: Journal of Biochemical and Molecular Toxicology
https://read.qxmd.com/read/30255456/synthetically-lethal-bmn-673-talazoparib-loaded-solid-lipid-nanoparticles-for-brca1-mutant-triple-negative-breast-cancer
#19
JOURNAL ARTICLE
Gamze Guney Eskiler, Gulsah Cecener, Unal Egeli, Berrin Tunca
PURPOSE: The purpose of the study was to produce BMN 673 loaded solid lipid nanoparticles (SLNs) to improve its therapeutic index, to minimize toxicity and to overcome homologous recombination (HR)-mediated resistance. METHODS: Firstly, BMN 673-SLNs were characterized using Nano Zeta Sizer. After treatment with different concentrations of BMN 673 and BMN 673-SLNs, cell viability of HCC1937(BRCA1-/-) , HCC1937-R (BMN 673-resistant) TNBC and MCF-10A normal human mammary breast epithelial cell line was analyzed by WST-1 assay...
September 25, 2018: Pharmaceutical Research
https://read.qxmd.com/read/30152517/parp-inhibitors-synergize-with-gemcitabine-by-potentiating-dna-damage-in-non-small-cell-lung-cancer
#20
JOURNAL ARTICLE
Yu Jiang, Hui Dai, Yang Li, Jun Yin, Shuliang Guo, Shiaw-Yih Lin, Daniel J McGrail
Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise in the treatment of patients with deficiencies in homologous recombination (HR) DNA repair, such as those with loss of BRCA1 or BRCA2 function. However, emerging studies suggest that PARP inhibition can also target HR-competent cancers, such as non-small-cell lung cancer (NSCLC), and that the therapeutic effect of PARP inhibition may be improved by combination with chemotherapy agents. In our study, it was found that PARP inhibitors talazoparib (BMN-673) and olaparib (AZD-2281) both had synergistic activity with the common first-line chemotherapeutic gemcitabine in a panel of lung cancer cell lines...
March 1, 2019: International Journal of Cancer. Journal International du Cancer
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