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(PDF) In vitro analysis of PARP inhibitor nanoformulations
<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="9vxi4TpscePAt6ymw2zTYEcjhcsrNLb-RL4v2Sg0URVSXAupT27yG_nXaxxsErdJsDx5tp6eigh7UzZmrCbnLQ" /> <meta name="citation_title" content="In vitro analysis of PARP inhibitor nanoformulations" /> <meta name="citation_publication_date" content="2018/01/01" /> <meta name="citation_journal_title" content="International journal of nanomedicine" /> <meta name="citation_author" content="Shifalika Tangutoori" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/62164278/In_vitro_analysis_of_PARP_inhibitor_nanoformulations" /> <meta name="twitter:title" content="In vitro analysis of PARP inhibitor nanoformulations" /> <meta name="twitter:description" content="PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an" /> <meta name="twitter:image" content="http://a.academia-assets.com/images/twitter-card.jpeg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/62164278/In_vitro_analysis_of_PARP_inhibitor_nanoformulations" /> <meta property="og:title" content="In vitro analysis of PARP inhibitor nanoformulations" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an" /> <meta property="article:author" content="https://independent.academia.edu/ShifalikaTangutoori" /> <meta name="description" content="PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an" /> <title>(PDF) In vitro analysis of PARP inhibitor nanoformulations</title> <link rel="canonical" href="https://www.academia.edu/62164278/In_vitro_analysis_of_PARP_inhibitor_nanoformulations" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = '129f474dbcc8e505390b0f49472dac75fb69884e'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1740155279000); window.Aedu.timeDifference = new Date().getTime() - 1740155279000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in an oral form and has poor bioavailability, consequently leading to poor accumulation in the tumor due to first-pass metabolism. Therefore, in the present study, an injectable nanoparticle formulation of olaparib was created that offers a delivery route in which the drug would be fully bioavailable in the vasculature, suggesting greater tumor accumulation. Our results illustrated that injectable nanoformulations of olaparib and BMN-673, a next generation PARPi, could be developed, and an efficacy test indicated that BMN-673 is a much more potent PARPi than olaparib. The success of these molecula...","author":[{"@context":"https://schema.org","@type":"Person","name":"Shifalika Tangutoori","url":"https://independent.academia.edu/ShifalikaTangutoori"}],"contributor":[],"dateCreated":"2021-11-22","dateModified":"2021-11-22","datePublished":"2018-01-01","headline":"In vitro analysis of PARP inhibitor nanoformulations","image":"https://attachments.academia-assets.com/75001054/thumbnails/1.jpg","inLanguage":"en","keywords":["Nanomedicine","Nanotechnology","Humans","Nanostructures","Drug Delivery Systems","Biological Availability","Antineoplastic Agents","Phthalazines","Pharmacology and pharmaceutical sciences"],"publication":"International journal of nanomedicine","publisher":{"@context":"https://schema.org","@type":"Organization","name":null},"sourceOrganization":[{"@context":"https://schema.org","@type":"EducationalOrganization","name":null}],"thumbnailUrl":"https://attachments.academia-assets.com/75001054/thumbnails/1.jpg","url":"https://www.academia.edu/62164278/In_vitro_analysis_of_PARP_inhibitor_nanoformulations"}</script><style type="text/css">@media(max-width: 567px){:root{--token-mode: Rebrand;--dropshadow: 0 2px 4px 0 #22223340;--primary-brand: #0645b1;--error-dark: #b60000;--success-dark: #05b01c;--inactive-fill: #ebebee;--hover: #0c3b8d;--pressed: #082f75;--button-primary-fill-inactive: #ebebee;--button-primary-fill: #0645b1;--button-primary-text: #ffffff;--button-primary-fill-hover: #0c3b8d;--button-primary-fill-press: #082f75;--button-primary-icon: #ffffff;--button-primary-fill-inverse: #ffffff;--button-primary-text-inverse: #082f75;--button-primary-icon-inverse: #0645b1;--button-primary-fill-inverse-hover: 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{"work":{"id":62164278,"created_at":"2021-11-22T02:23:40.095-08:00","from_world_paper_id":184482549,"updated_at":"2021-11-22T02:47:17.580-08:00","_data":{"abstract":"PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in an oral form and has poor bioavailability, consequently leading to poor accumulation in the tumor due to first-pass metabolism. Therefore, in the present study, an injectable nanoparticle formulation of olaparib was created that offers a delivery route in which the drug would be fully bioavailable in the vasculature, suggesting greater tumor accumulation. Our results illustrated that injectable nanoformulations of olaparib and BMN-673, a next generation PARPi, could be developed, and an efficacy test indicated that BMN-673 is a much more potent PARPi than olaparib. The success of these molecula...","publication_date":"2018,,","publication_name":"International journal of nanomedicine"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"In vitro analysis of PARP inhibitor nanoformulations","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [55342623]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":75001054,"attachmentType":"pdf"}"><img alt="First page of “In vitro analysis of PARP inhibitor nanoformulations”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/75001054/mini_magick20211122-19796-3f4az5.png?1637576931" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">In vitro analysis of PARP inhibitor nanoformulations</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="55342623" href="https://independent.academia.edu/ShifalikaTangutoori"><img alt="Profile image of Shifalika Tangutoori" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Shifalika Tangutoori</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2018, International journal of nanomedicine</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">3 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 62164278; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in an oral form and has poor bioavailability, consequently leading to poor accumulation in the tumor due to first-pass metabolism. Therefore, in the present study, an injectable nanoparticle formulation of olaparib was created that offers a delivery route in which the drug would be fully bioavailable in the vasculature, suggesting greater tumor accumulation. Our results illustrated that injectable nanoformulations of olaparib and BMN-673, a next generation PARPi, could be developed, and an efficacy test indicated that BMN-673 is a much more potent PARPi than olaparib. The success of these molecula...</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":75001054,"attachmentType":"pdf","workUrl":"https://www.academia.edu/62164278/In_vitro_analysis_of_PARP_inhibitor_nanoformulations"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":75001054,"attachmentType":"pdf","workUrl":"https://www.academia.edu/62164278/In_vitro_analysis_of_PARP_inhibitor_nanoformulations"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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Here we show that radiation-resistant cells and tumors derived from a Pten/Trp53-deficient mouse model of advanced prostate cancer are rendered radiation-sensitive following treatment with NanoOlaparib, a lipid-based injectable nanoformulation of Olaparib. This enhancement in radiosensitivity is accompanied by radiation dose-dependent changes in γ-H2AX expression and is specific to NanoOlaparib alone. In animals, twice-weekly intravenous administration of NanoOlaparib results in significant tumor growth inhibition, whereas previous studies of oral Olaparib as monotherapy have shown no therapeutic efficacy. When NanoOlaparib is administered prior to radiation, a single dose of radiation is sufficient to triple the median mouse survival time compared to radiation only controls. Half of mice treated with NanoOlaparib + radiation achieved a complete response over the 13 week study duration. Using ferumoxytol as a surrogate nanoparticle, MRI studies revealed that NanoOlaparib enhances the intratumoral accumulation of systemically administered nanoparticles. NanoOlaparib-treated tumors showed up to 19-fold higher nanoparticle accumulation compared to untreated and radiation-only controls, suggesting that the in vivo efficacy of NanoOlaparib may be potentiated by its ability to enhance its own accumulation. Together, this data suggests that</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53- Deficient Prostate Cancer to Radiation","attachmentId":75001053,"attachmentType":"pdf","work_url":"https://www.academia.edu/62164276/Nanoformulation_of_Olaparib_Amplifies_PARP_Inhibition_and_Sensitizes_PTEN_TP53_Deficient_Prostate_Cancer_to_Radiation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/62164276/Nanoformulation_of_Olaparib_Amplifies_PARP_Inhibition_and_Sensitizes_PTEN_TP53_Deficient_Prostate_Cancer_to_Radiation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="89157938" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/89157938/A_Very_Long_Acting_PARP_Inhibitor_Suppresses_Cancer_Cell_Growth_in_DNA_Repair_Deficient_Tumor_Models">A Very Long-Acting PARP Inhibitor Suppresses Cancer Cell Growth in DNA Repair-Deficient Tumor Models</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="242003659" href="https://independent.academia.edu/RyanNguyen196">Ryan Nguyen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Research, 2020</p><p class="ds-related-work--abstract ds2-5-body-sm">PARP inhibitors are approved for treatment of cancers with BRCA1 or BRCA2 defects. In this study, we prepared and characterized a very long-acting PARP inhibitor. Synthesis of a macromolecular prodrug of talazoparib (TLZ) was achieved by covalent conjugation to a PEG40kDa carrier via a β-eliminative releasable linker. A single injection of the PEG∼TLZ conjugate was as effective as ∼30 daily oral doses of TLZ in growth suppression of homologous recombination-defective tumors in mouse xenografts. These included the KT-10 Wilms&#39; tumor with a PALB2 mutation, the BRCA1-deficient MX-1 triple-negative breast cancer, and the BRCA2-deficient DLD-1 colon cancer; the prodrug did not inhibit an isogenic DLD-1 tumor with wild-type BRCA2. Although the half-life of PEG∼TLZ and released TLZ in the mouse was only ∼1 day, the exposure of released TLZ from a single safe, effective dose of the prodrug exceeded that of oral TLZ given daily over one month. μPET/CT imaging showed high uptake and prolo...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A Very Long-Acting PARP Inhibitor Suppresses Cancer Cell Growth in DNA Repair-Deficient Tumor Models","attachmentId":93008919,"attachmentType":"pdf","work_url":"https://www.academia.edu/89157938/A_Very_Long_Acting_PARP_Inhibitor_Suppresses_Cancer_Cell_Growth_in_DNA_Repair_Deficient_Tumor_Models","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/89157938/A_Very_Long_Acting_PARP_Inhibitor_Suppresses_Cancer_Cell_Growth_in_DNA_Repair_Deficient_Tumor_Models"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="83710924" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/83710924/Intracellular_Pharmacokinetics_of_PARP_Inhibitors_in_Breast_and_Ovarian_Cancer_Cells_and_Correlation_to_Drug_Action_A_Review">Intracellular Pharmacokinetics of PARP Inhibitors in Breast and Ovarian Cancer Cells and Correlation to Drug Action: A Review</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="133277036" href="https://independent.academia.edu/MARGARETPHIRI5">MARGARET PHIRI</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Pharmaceutics & Pharmacology, 2020</p><p class="ds-related-work--abstract ds2-5-body-sm">Recently Poly (ADP-Ribose) Polymerase inhibitor (PARPi) drugs were approved by the FDA for clinical use in breast and ovarian cancer, recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. Olaparib an oral formulation approved for the treatment of patients with BRCA mutation and recurrent ovarian cancer; has shown to provide clinically significant benefit. Inhibition of PARP results in accumulation of single-strand breaks, leading to formation of double-strand breaks. Olaparib, a small molecule, selectively binds and inhibits Poly (ADP-Ribose) Polymerase enzyme, inhibiting its mediated repair of single-strand DNA breaks. Poly (ADP-Ribose) Polymerase inhibition enhances cytotoxicity of DNA damaging agents and reverses tumor cell chemoresistance and radio resistance. There has been limited research on the quantification of anti-cancer drugs intracellularly; very few studies have attempted to quantify Olaparib intracellularly. For the first time, intercellular quantification of PARP inhibitor was reported in two studies involving oral dosage form and the other nano-delivery system, allowing for quantification of Olaparib distribution in the nuclei, cytoplasm, liver, kidney, plasma, and urine. This review, covers articles and reports from 1992 to 2019 and is aimed at highlighting the increasing importance of intracellular quantification of anti-cancer drugs using PARP inhibitors as examples, due to limited research done on this group of drugs, only Olaparib has been reported have been determined intracellularly.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Intracellular Pharmacokinetics of PARP Inhibitors in Breast and Ovarian Cancer Cells and Correlation to Drug Action: A Review","attachmentId":88966947,"attachmentType":"pdf","work_url":"https://www.academia.edu/83710924/Intracellular_Pharmacokinetics_of_PARP_Inhibitors_in_Breast_and_Ovarian_Cancer_Cells_and_Correlation_to_Drug_Action_A_Review","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/83710924/Intracellular_Pharmacokinetics_of_PARP_Inhibitors_in_Breast_and_Ovarian_Cancer_Cells_and_Correlation_to_Drug_Action_A_Review"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="54119620" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/54119620/Active_Targeted_Nanoparticles_for_Delivery_of_Poly_ADP_ribose_Polymerase_PARP_Inhibitors_A_Preliminary_Review">Active Targeted Nanoparticles for Delivery of Poly(ADP-ribose) Polymerase (PARP) Inhibitors: A Preliminary Review</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51659095" href="https://yeungnam.academia.edu/SadanandPandey">Sadanand Pandey</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Molecular Sciences</p><p class="ds-related-work--abstract ds2-5-body-sm">Nanotechnology has revolutionized novel drug delivery strategies through establishing nanoscale drug carriers, such as niosomes, liposomes, nanomicelles, dendrimers, polymeric micelles, and nanoparticles (NPs). Owing to their desirable cancer-targeting efficacy and controlled release, these nanotherapeutic modalities are broadly used in clinics to improve the efficacy of small-molecule inhibitors. Poly(ADP-ribose) polymerase (PARP) family members engage in various intracellular processes, including DNA repair, gene transcription, signal transduction, cell cycle regulation, cell division, and antioxidant response. PARP inhibitors are synthetic small-molecules that have emerged as one of the most successful innovative strategies for targeted therapy in cancer cells harboring mutations in DNA repair genes. Despite these advances, drug resistance and unwanted side effects are two significant drawbacks to using PARP inhibitors in the clinic. Recently, the development of practical nanotec...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Active Targeted Nanoparticles for Delivery of Poly(ADP-ribose) Polymerase (PARP) Inhibitors: A Preliminary Review","attachmentId":70638330,"attachmentType":"pdf","work_url":"https://www.academia.edu/54119620/Active_Targeted_Nanoparticles_for_Delivery_of_Poly_ADP_ribose_Polymerase_PARP_Inhibitors_A_Preliminary_Review","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/54119620/Active_Targeted_Nanoparticles_for_Delivery_of_Poly_ADP_ribose_Polymerase_PARP_Inhibitors_A_Preliminary_Review"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="594286" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/594286/PARP_Inhibitor_as_an_Effective_Standard_Treatment_in_Cancer_with_DNA_Repair_Defects">PARP Inhibitor as an Effective Standard Treatment in Cancer with DNA Repair Defects</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="300429" href="https://wustl.academia.edu/StephanieSandvickWeyrauch">Stephanie Weyrauch</a></div><p class="ds-related-work--abstract ds2-5-body-sm">Today breast cancer is the second most diagnosed cancer in women, accounting for 1 in 4 cancers diagnosed. Some oncologists have suggested that the poor prognosis of certain cancers may be blamed on current standardized cancer treatments. PARP inhibitor, an anticancer drug that affects base excision repair in DNA of cancer cells has been a proposed solution to increasing cancer survival rates when used in conjunction with standardized cancer treatments. This speech discusses the problems associated with standardized cancer treatments and how PARP inhibitor can be a contributor to maximize these treatments.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"PARP Inhibitor as an Effective Standard Treatment in Cancer with DNA Repair Defects","attachmentId":3117869,"attachmentType":"pdf","work_url":"https://www.academia.edu/594286/PARP_Inhibitor_as_an_Effective_Standard_Treatment_in_Cancer_with_DNA_Repair_Defects","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/594286/PARP_Inhibitor_as_an_Effective_Standard_Treatment_in_Cancer_with_DNA_Repair_Defects"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="103333495" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/103333495/Nanoparticle_mediated_delivery_of_siRNA_targeting_Parp1_extends_survival_of_mice_bearing_tumors_derived_from_Brca1_deficient_ovarian_cancer_cells">Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="226572218" href="https://independent.academia.edu/NGajanayaka">Niranjala Gajanayaka</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Proceedings of the National Academy of Sciences, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) with small molecules has been shown to be an effective treatment for ovarian cancer with BRCA mutations. Here, we report the in vivo administration of siRNA to Parp1 in mouse models of ovarian cancer. A unique member of the lipid-like materials known as lipidoids is shown to deliver siRNA to disseminated murine ovarian carcinoma allograft tumors following intraperitoneal (i.p.) injection. siParp1 inhibits cell growth, primarily by induction of apoptosis, in Brca1-deficient cells both in vitro and in vivo. Additionally, the treatment extends the survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells but not from Brca1 wild-type cells, confirming the proposed mechanism of synthetic lethality. Because there are 17 members of the Parp family, the inherent complementarity of RNA affords a high level of specificity for therapeutically addressing Parp1 in the context of impaired homologous ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Nanoparticle-mediated delivery of siRNA targeting Parp1 extends survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells","attachmentId":103368565,"attachmentType":"pdf","work_url":"https://www.academia.edu/103333495/Nanoparticle_mediated_delivery_of_siRNA_targeting_Parp1_extends_survival_of_mice_bearing_tumors_derived_from_Brca1_deficient_ovarian_cancer_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/103333495/Nanoparticle_mediated_delivery_of_siRNA_targeting_Parp1_extends_survival_of_mice_bearing_tumors_derived_from_Brca1_deficient_ovarian_cancer_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="83929503" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/83929503/A_Review_on_DNA_Repair_Inhibition_by_PARP_Inhibitors_in_Cancer_Therapy">A Review on DNA Repair Inhibition by PARP Inhibitors in Cancer Therapy</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="148429686" href="https://mu.academia.edu/ShahAshish">Ashish Shah</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Folia medica, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">The DNA repair process protects the cells from DNA damaging agent by multiple pathways. Majority of the cancer therapy cause DNA damage which leads to apoptosis. The cell has natural ability to repair this damage which ultimately leads to development of resistance of drugs. The key enzymes involved in DNA repair process are poly(ADP-ribose) (PAR) and poly(ADP-ribose) polymerases (PARP). Tumor cells repair their defective gene via defective homologues recombination (HR) in the presence of enzyme PARP. PARP inhibitors inhibit the enzyme poly(ADP-ribose) polymerases (PARPs) which lead to apoptosis of cancer cells. Current clinical data shows the role of PARP inhibitors is not restricted to BRCA mutations but also effective in HR dysfunctions related tumors. Therefore, investigation in this area could be very helpful for future therapy of cancer. This review gives detail information on the role of PARP in DNA damage repair, the role of PARP inhibitors and chemistry of currently availabl...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A Review on DNA Repair Inhibition by PARP Inhibitors in Cancer Therapy","attachmentId":89118824,"attachmentType":"pdf","work_url":"https://www.academia.edu/83929503/A_Review_on_DNA_Repair_Inhibition_by_PARP_Inhibitors_in_Cancer_Therapy","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/83929503/A_Review_on_DNA_Repair_Inhibition_by_PARP_Inhibitors_in_Cancer_Therapy"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="43435415" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/43435415/PARP_Inhibitors_in_Cancer_Therapy_Magic_Bullets_but_Moving_Targets">PARP Inhibitors in Cancer Therapy: Magic Bullets but Moving Targets</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="162124620" href="https://independent.academia.edu/pinkimehta4">pinki mehta</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Oncology, 2013</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"PARP Inhibitors in Cancer Therapy: Magic Bullets but Moving Targets","attachmentId":63743939,"attachmentType":"pdf","work_url":"https://www.academia.edu/43435415/PARP_Inhibitors_in_Cancer_Therapy_Magic_Bullets_but_Moving_Targets","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/43435415/PARP_Inhibitors_in_Cancer_Therapy_Magic_Bullets_but_Moving_Targets"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="91878794" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/91878794/Nanoemulsion_Based_Delivery_of_Fluorescent_PARP_Inhibitors_in_Mouse_Models_of_Small_Cell_Lung_Cancer">Nanoemulsion-Based Delivery of Fluorescent PARP Inhibitors in Mouse Models of Small Cell Lung Cancer</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="247811655" href="https://independent.academia.edu/JuniorGonzales33">Junior Gonzales</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Bioconjugate Chemistry, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">The preclinical potential of many diagnostic and therapeutic small molecules is limited by their rapid washout kinetics and consequently modest pharmacological performances. In several cases, these could be improved by loading the small molecules into nanoparticulates, improving blood half-life, in vivo uptake and overall pharmacodynamics. In this study, we report a nanoemulsion (NE) encapsulated form of PARPi-FL. As a proof of concept, we used PARPi-FL, which is a fluorescently labeled sensor for olaparib, a FDA-approved small molecule inhibitor of the nuclear enzyme poly(ADP-ribose)polymerase 1 (PARP1). Encapsulated PARPi-FL showed increased blood half-life, and delineated subcutaneous xenografts of small cell lung cancer (SCLC), a fastprogressing disease where effcient treatment options remain an unmet clinical need. Our study demonstrates an effective method for expanding the circulation time of a fluorescent PARP inhibitor, highlighting the pharmacokinetic benefits of nanoemulsions as nanocarriers and confirming the value of PARPi-FL as an imaging agent targeting PARP1 in small cell lung cancer.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Nanoemulsion-Based Delivery of Fluorescent PARP Inhibitors in Mouse Models of Small Cell Lung Cancer","attachmentId":95040791,"attachmentType":"pdf","work_url":"https://www.academia.edu/91878794/Nanoemulsion_Based_Delivery_of_Fluorescent_PARP_Inhibitors_in_Mouse_Models_of_Small_Cell_Lung_Cancer","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/91878794/Nanoemulsion_Based_Delivery_of_Fluorescent_PARP_Inhibitors_in_Mouse_Models_of_Small_Cell_Lung_Cancer"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="29143544" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/29143544/Therapeutic_applications_of_PARP_inhibitors_Anticancer_therapy_and_beyond">Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="54883966" href="https://independent.academia.edu/NicolaCurtin">Nicola Curtin</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular Aspects of Medicine, 2013</p><p class="ds-related-work--abstract ds2-5-body-sm">The aim of this article is to describe the current and potential clinical translation of pharmacological inhibitors of poly(ADP-ribose) polymerase (PARP) for the therapy of various diseases. The first section of the present review summarizes the available preclinical and clinical data with PARP inhibitors in various forms of cancer. In this context, the role of PARP in single-strand DNA break repair is relevant, leading to replication-associated lesions that cannot be repaired if homologous recombination repair (HRR) is defective, and the synthetic lethality of PARP inhibitors in HRR-defective cancer. HRR defects are classically associated with BRCA1 and 2 mutations associated with familial breast and ovarian cancer, but there may be many other causes of HRR defects. Thus, PARP inhibitors may be the drugs of choice for BRCA mutant breast and ovarian cancers, and extend beyond these tumors if appropriate biomarkers can be developed to identify HRR defects. Multiple lines of preclinical data demonstrate that PARP inhibition increases cytotoxicity and tumor growth delay in combination with temozolomide, topoisomerase inhibitors and ionizing radiation. Both single agent and combination clinical trials are underway. The final part of the first section of the present review summarizes the current status of the various PARP inhibitors that are in various stages of clinical development. The second section of the present review summarizes the role of PARP in selected non-oncologic indications. In a number of severe, acute diseases (such as stroke, neurotrauma, circulatory shock and acute myocardial infarction) the clinical translatability of PARP inhibition is supported by multiple lines of preclinical data, as well as observational data demonstrating PARP activation in human tissue samples. In these disease indications, PARP overactivation due to oxidative and nitrative stress drives cell necrosis and pro-inflammatory gene expression, which contributes to disease pathology. Accordingly, multiple lines of preclinical data indicate the efficacy of PARP inhibitors to preserve viable tissue and to down-regulate inflammatory responses. As the clinical trials with PARP inhibitors in various forms of cancer progress, it is hoped that a second line of clinical investigations, aimed at testing of PARP inhibitors for various non-oncologic indications, will be initiated, as well.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond","attachmentId":49590205,"attachmentType":"pdf","work_url":"https://www.academia.edu/29143544/Therapeutic_applications_of_PARP_inhibitors_Anticancer_therapy_and_beyond","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/29143544/Therapeutic_applications_of_PARP_inhibitors_Anticancer_therapy_and_beyond"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":75001054,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":75001054,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_75001054" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="39855809" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/39855809/Quantitative_Characterization_of_Olaparib_in_Nanodelivery_System_and_Target_Cell_Compartments_by_LC_MS_MS">Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="24340269" href="https://unimi.academia.edu/MatteoMiceli">Matteo Miceli</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecules, 2019</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS","attachmentId":60041561,"attachmentType":"pdf","work_url":"https://www.academia.edu/39855809/Quantitative_Characterization_of_Olaparib_in_Nanodelivery_System_and_Target_Cell_Compartments_by_LC_MS_MS","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/39855809/Quantitative_Characterization_of_Olaparib_in_Nanodelivery_System_and_Target_Cell_Compartments_by_LC_MS_MS"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="1" data-entity-id="109877230" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/109877230/Enhanced_Antitumoral_Activity_of_Encapsulated_BET_Inhibitors_When_Combined_with_PARP_Inhibitors_for_the_Treatment_of_Triple_Negative_Breast_and_Ovarian_Cancers">Enhanced Antitumoral Activity of Encapsulated BET Inhibitors When Combined with PARP Inhibitors for the Treatment of Triple-Negative Breast and Ovarian Cancers</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="277253982" href="https://independent.academia.edu/AlbertoJuan20">Alberto Juan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancers</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Enhanced Antitumoral Activity of Encapsulated BET Inhibitors When Combined with PARP Inhibitors for the Treatment of Triple-Negative Breast and Ovarian Cancers","attachmentId":107869084,"attachmentType":"pdf","work_url":"https://www.academia.edu/109877230/Enhanced_Antitumoral_Activity_of_Encapsulated_BET_Inhibitors_When_Combined_with_PARP_Inhibitors_for_the_Treatment_of_Triple_Negative_Breast_and_Ovarian_Cancers","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/109877230/Enhanced_Antitumoral_Activity_of_Encapsulated_BET_Inhibitors_When_Combined_with_PARP_Inhibitors_for_the_Treatment_of_Triple_Negative_Breast_and_Ovarian_Cancers"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="95131410" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/95131410/PARP_inhibitors_its_role_in_treatment_of_cancer">PARP inhibitors: its role in treatment of cancer</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32570215" href="https://independent.academia.edu/AliceChen23">Alice Chen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Chinese Journal of Cancer, 2011</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"PARP inhibitors: its role in treatment of cancer","attachmentId":97397660,"attachmentType":"pdf","work_url":"https://www.academia.edu/95131410/PARP_inhibitors_its_role_in_treatment_of_cancer","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/95131410/PARP_inhibitors_its_role_in_treatment_of_cancer"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="3" data-entity-id="67116599" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/67116599/Mechanistic_Dissection_of_PARP1_Trapping_and_the_Impact_on_in_vivo_Tolerability_and_Efficacy_of_PARP_Inhibitors">Mechanistic Dissection of PARP1 Trapping and the Impact on in vivo Tolerability and Efficacy of PARP Inhibitors</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="157654845" href="https://independent.academia.edu/luisrodriguez2418">luis rodriguez</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular cancer research : MCR, 2015</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" 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