[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382550-105":59,"doc-detail-382550-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","targeting-dna-repair-for-cancer-treatment-lessons-from-parp-inhibitor-trials","Targeting DNA repair for cancer treatment - Lessons from PARP inhibitor trials","","Ionizing radiation is widely used to treat solid tumors by inducing DNA damage that kills cancer cells. Resistance emerges because damaged DNA can be repaired through poly-(ADP-ribose) polymerase-1 (PARP-1) activity, making PARP-1 an important therapeutic target across multiple cancer types, including prostate cancer. PARP is essential for repairing single-strand DNA breaks, and PARP-1 inhibition is lethal in many cancer cells lacking homologous recombination repair (HR).",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/targeting-dna-repair-for-cancer-treatment-lessons-from-parp-inhibitor-trials/382550/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/targeting-dna-repair-for-cancer-treatment-lessons-from-parp-inhibitor-trials/382550.png","ImageObject",300,407,{"name":92,"@type":93},"Connor ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why does PARP-1 inhibition matter in radiotherapy for solid tumors?","Question",{"text":113,"@type":114},"Radiation creates DNA damage, but PARP-1-mediated repair can reduce the therapy effect. Blocking PARP-1 can hinder this repair and improve treatment targeting.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is PARylation and how does it relate to DNA repair?",{"text":118,"@type":114},"PARP enzymes catalyze formation of poly-ADP-ribose chains on target proteins and can also self-PARylate. This process alters protein charge and supports recruitment of repair factors at DNA breaks.",{"name":120,"@type":111,"acceptedAnswer":121},"How does synthetic lethality support PARP inhibitor use in cancer?",{"text":122,"@type":114},"Cells with defective homologous recombination repair can be killed when PARP-1 is inhibited. The combined failure of two repair-dependent functions leads to cell death.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},382550,1790342318,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},687207022233,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","ONCOLOGY RESEARCH 2023 31(4): 405-421  \nTargeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials  \nDHANYA K. NAMBIAR1; DEEPALI MISHRA2; RANA P. SINGH2,3,*  \n1 Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 94305, USA  \n2 Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India  \n3 Special Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, 10067, India Key words: PARP inhibitors, Synthetic lethality, DNA repair, BRCA mutations  \nAbstract: Ionizing radiation is frequently used to treat solid tumors, as it causes DNA damage and kill cancer cells.  \nHowever, damaged DNA is repaired involving poly-(ADP-ribose) polymerase-1 (PARP-1) causing resistance to radiation therapy. Thus, PARP-1 represents an important target in multiple cancer types, including prostate cancer.  \nPARP is a nuclear enzyme essential for single-strand DNA breaks repair. Inhibiting PARP-1 is lethal in a wide range of cancer cells that lack the homologous recombination repair (HR) pathway. This article provides a concise and simplified overview of the development of PARP inhibitors in the laboratory and their clinical applications. We focused on the use of PARP inhibitors in various cancers, including prostate cancer. We also discussed some of the  \nunderlying principles and challenges that may affect the clinical efficacy of PARP inhibitors.  \nIntroduction  \nDNA repair pathways in normal cells ensure error-free replication and maintain genomic integrity. However, it is known that DNA repair genes are frequently mutated in cancer which contributes significantly to cancer development and progression [1] . DNA repair dysfunction is an ideal ally for the cancer cells to acquire an aggressive phenotype and therapeutic resistance [2,3]. Our cells utilize multiple different mechanisms of DNA repair based on the kind of lesioninduced. These include direct repair, mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER), and double-strand break (DSB) recombinational repair, which encompasses both non-homologous end-joining (NHEJ) and homologous recombinational repair (HR) . This remarkable redundancy in the DNA repair pathway is in place to ensure precision in the process of DNA replication. This also guarantees that the cells have a second chance to survive, even if one of these pathways fails.  \nDuring cancer development, the cells continue to acquire different mutations, not only due to defects in DNA repair/ genomic instability but also due to poor redox balance in  \n*Address correspondence to: Rana P. Singh, [rana_singh@mail.jnu.ac.in](rana_singh@mail.jnu.ac.in)  \nReceived: 11 December 2022; Accepted: 21 March 2023;  \nPublished: 27 June 2023  \nthese cells. The poorly functioning redox regulation causes these cells to have higher oxidative stress. The sustained oxidative stress leads to significant oxidative DNA damage, which further contributes to genomic instability and higher mutational burden [4] . In this context, the same backup repair pathways assist them to remain viable and repair the damage caused by chemotherapeutic or other genotoxic agents used for treatment. Given that the cancers with defective DNA repair genes rely on alternative pathways, it was correctly hypothesized that further blocking of the other DNA repair pathways would be lethal for these cells. The concept of “synthetic lethality” [5], which describes a situation “where a defect in one gene is compatible with cell viability but results in cell death when combined with a defect in another gene”, has thus formed the basis of newer targeted therapies especially focusing the DNA repair pathways in cancers [6] .  \nExploiting Synthetic Lethality Approach for Cancer Treatment  \nThough synthetic lethality was established decades earlier, the potential of this approach for drug targeting in cancer was only harnessed in recent years, due to a lack of r","cbCaidtWBHzUbxoD","https://ap.wps.com/l/cbCaidtWBHzUbxoD","pdf",1978542,17,"English","# Introduction\n## DNA repair pathways and therapeutic resistance\n# Exploiting Synthetic Lethality Approach for Cancer Treatment\n# The Promise of PARP Inhibitors","[{\"question\":\"Why does PARP-1 inhibition matter in radiotherapy for solid tumors?\",\"answer\":\"Radiation creates DNA damage, but PARP-1-mediated repair can reduce the therapy effect. Blocking PARP-1 can hinder this repair and improve treatment targeting.\"},{\"question\":\"What is PARylation and how does it relate to DNA repair?\",\"answer\":\"PARP enzymes catalyze formation of poly-ADP-ribose chains on target proteins and can also self-PARylate. This process alters protein charge and supports recruitment of repair factors at DNA breaks.\"},{\"question\":\"How does synthetic lethality support PARP inhibitor use in cancer?\",\"answer\":\"Cells with defective homologous recombination repair can be killed when PARP-1 is inhibited. The combined failure of two repair-dependent functions leads to cell death.\"}]","Targeting DNA repair for cancer treatment - Lessons from PARP inhibitor trials | PDF",1790250963,43]