[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-356931-105":59,"doc-detail-356931-en":129},{"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":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","natural-g-quadruplex-stabilizers-a-targeted-strategy-for-breast-cancer-therapy","Natural G-Quadruplex Stabilizers - A Targeted Strategy for Breast Cancer Therapy","","G-quadruplexes (G4s) are non-canonical DNA structures central to gene regulation, telomere repair, and cancer biology. Breast cancer G4s are enriched at promoters of key oncogenes, making them actionable therapeutic targets. While synthetic stabilizers are studied, natural products are a less explored source of selective, biocompatible, multi-target ligands. This review compiles natural compounds that stabilize G4s, details interaction mechanisms and genomic mapping, and highlights gaps in in vivo validation, subtype efficacy, and pharmacokinetics, proposing a roadmap for future discovery.",{"@graph":69,"@context":121},[70,84,104],{"@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/natural-g-quadruplex-stabilizers-a-targeted-strategy-for-breast-cancer-therapy/356931/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/natural-g-quadruplex-stabilizers-a-targeted-strategy-for-breast-cancer-therapy/356931.png","ImageObject",300,407,{"name":92,"@type":93},"McQueen","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23",true,{"@type":101,"interactionType":102,"userInteractionCount":4},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What makes G-quadruplexes (G4s) relevant for cancer therapy?","Question",{"text":111,"@type":112},"G4s participate in gene regulation, telomere repair, nucleic acid metabolism, and genomic integrity. In genes, they function as regulatory factors linked to cancer processes, so they can be targeted therapeutically.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"Why are G4s considered promising targets in breast cancer?",{"text":116,"@type":112},"Breast cancer G4s are enriched in promoters of oncogenes such as c-MYC, KRAS, BCL2, HER2, and ESR1, and mapping shows they cluster around key regulatory genomic regions like promoters and first introns near transcription start sites.",{"name":118,"@type":109,"acceptedAnswer":119},"What limitations exist in current evidence for natural G4 stabilizers in breast cancer?",{"text":120,"@type":112},"Key gaps include limited in vivo validation, subtype-specific efficacy data being insufficient, and unresolved pharmacokinetic issues. As a result, effectiveness is constrained by the lack of thorough subtype-resolved and in vivo studies.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},356931,1790128325,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":4,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":128,"read_time":143},5909890329169,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Drug Design, Development and Therapy  \n Open Access Full Text Article  \nREVIEW  \nNatural G-Quadruplex Stabilizers: A Targeted Strategy for Breast Cancer Therapy  \nChengjian Cao 1 , Chaoxiang Lv 2 , Ali ElFar 2  \n1Zigong Academy of Medical Sciences, Zigong First People’s Hospital, Zigong, Sichuan, People’s Republic of China; 2Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China  \nCorrespondence: Ali ElFar; Chaoxiang Lv, Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email [alih.elfar2024@swmu.edu.cn](alih.elfar2024@swmu.edu.cn); [lvchaoxiang@swmu.edu.cn](lvchaoxiang@swmu.edu.cn)  \n\n| Abstract: G-quadruplexes (G4s) are non-canonical DNA structures that are important in gene regulation, telomere repair, and cancer. The G4s in breast cancer (BC) are enriched in the promoters of important oncogenes, such as c-MYC, KRAS, BCL2, HER2, and ESR1, which are good therapeutic targets. Although synthetic G4 stabilizers are well-researched, natural products are a poorly investigated source of selective ligands with good biocompatibility and multi-target properties. This review systematically collects and analyzes natural compounds, such as flavonoids, alkaloids, polyphenols, terpenoids, and organosulfur compounds, which exhibit G4-stabilizing effects, particularly their suitability in BC. We provide a comprehensive landscape approach to define interactions between G4-ligands, discuss how these interactions are stabilized (via π-π stacking, electrostatic interactions, and groove binding), and map these compounds to genomic regions associated with BC G4-formation. We also identify key research gaps that are essential, including limited in vivo validation, subtype-specific efficacy, and pharmacokinetic issues. The available evidence suggests that natural G4 stabilizers have potential as multi-target and biocompatible agents for BC therapy. However, their effectiveness is currently constrained by a shortage of thorough in vivo studies and subtype-specific data. Lastly, to incorporate in silico docking, mechanistic studies, and translational strategies, we present a prospective roadmap for drug discovery to bring natural G4 stabilizers targeting BC. Keywords: G-quadruplexes, breast cancer, G4 stabilizers, natural products, drug discovery, future roadmap |\n| --- |\n| Introduction\u003Cbr>G-quadruplexes (G4s) consist of a G-tetrad, the square-planar structure of four guanine bases, forming quartets, 1 stabilized by Hoogsteen hydrogen bonding, which allows the tetrad to stack with other two or more tetrads to create G4s, and stabilized by the presence of cations, such as K+, Na+, and Li+ .2 Those guanine bases that are connected by hydrogen bonds between the N1, N7, O6, and N2 atoms of the guanine molecules form a G-tetrad between adjacent bases,3 as shown in Figure 1. G4s occur in great numbers in both prokaryotic and eukaryotic genomes and are vital for telomere maintenance, nucleic acid metabolism, and genomic integrity.4 G4s within genes are regulatory factors involved in cellular processes and pathogenesis, including cancer. They are therefore considered therapeutic targets in cancer treatment. G4s are essential for gene expression and DNA replication. The first G4s were reported in a study in 1962, and G4 tetrameric structures had been reported to form with their unique composition.5 They have, since that time, served asa model of research on their structural features and functional role in health processes and diseases.3\u003Cbr>The importance of targeting G4s in breast cancer (BC) is profound and exhibits unique features that distinguish it from other cancer types. BC is still the top cause of cancer death among women globally, and resistance to treatment—especially in triple-negative breast cancer (TNBC)—remains a major obstac","cbCaigcj7s8fSfWL","https://ap.wps.com/l/cbCaigcj7s8fSfWL","pdf",5491387,23,"English","# Introduction\n## G-quadruplex structure and biological roles\n## Targeting G4s in breast cancer","[{\"question\":\"What makes G-quadruplexes (G4s) relevant for cancer therapy?\",\"answer\":\"G4s participate in gene regulation, telomere repair, nucleic acid metabolism, and genomic integrity. In genes, they function as regulatory factors linked to cancer processes, so they can be targeted therapeutically.\"},{\"question\":\"Why are G4s considered promising targets in breast cancer?\",\"answer\":\"Breast cancer G4s are enriched in promoters of oncogenes such as c-MYC, KRAS, BCL2, HER2, and ESR1, and mapping shows they cluster around key regulatory genomic regions like promoters and first introns near transcription start sites.\"},{\"question\":\"What limitations exist in current evidence for natural G4 stabilizers in breast cancer?\",\"answer\":\"Key gaps include limited in vivo validation, subtype-specific efficacy data being insufficient, and unresolved pharmacokinetic issues. As a result, effectiveness is constrained by the lack of thorough subtype-resolved and in vivo studies.\"}]","Natural G-Quadruplex Stabilizers - A Targeted Strategy for Breast Cancer Therapy | PDF",58]