[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-350029-105":59,"doc-detail-350029-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","lk-1-an-investigational-therapy-targeting-hcg-in-metastatic-breast-bladder-ovarian-and-cervical-cancers","LK-1 - an investigational therapy targeting hCG-β in metastatic breast, bladder, ovarian, and cervical cancers","","Human chorionic gonadotropin beta (hCG-β), linked to poor cancer prognosis, is targeted by antisense phosphorodiamidate morpholino oligomers (PMO) to reduce hCG-β production at the mRNA transcript level. Multiple PMO sequences were screened using cell viability assays, pregnancy test strips, and ELISA, identifying LK-1 as the best candidate. Across nineteen sequences tested in eight cell lines, seven consistently lowered viability. LK-1 significantly reduced hCG-β expression by western blot and ELISA, decreased clonogenicity, increased cancer cell death, reduced invasion, and suppressed tumor formation in 3D spheroids, supporting morpholino-based therapy for hCG-β–expressing cancers.",{"@graph":69,"@context":122},[70,84,105],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/lk-1-an-investigational-therapy-targeting-hcg-in-metastatic-breast-bladder-ovarian-and-cervical-cancers/350029/",{"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/lk-1-an-investigational-therapy-targeting-hcg-in-metastatic-breast-bladder-ovarian-and-cervical-cancers/350029.png","ImageObject",300,407,{"name":92,"@type":93},"Jake","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why target hCG-β in metastatic cancers?","Question",{"text":112,"@type":113},"hCG-β is associated with aggressive, metastatic disease and poorer clinical outcomes. It has also been linked to treatment resistance and multiple cancer-promoting processes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were PMO sequences for hCG-β designed and screened?",{"text":117,"@type":113},"Researchers tested multiple PMO sequences against hCG-β mRNA transcripts across different regions. Knockdown was evaluated using cell viability assays, pregnancy test strips, and ELISA, followed by comparison of phenotype effects across concentrations.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence supports LK-1 as the most effective candidate?",{"text":121,"@type":113},"LK-1 significantly reduced hCG-β expression measured by western blot and ELISA. It also lowered cancer cell viability, clonogenicity, increased tumor cell death, reduced invasion, and reduced tumor formation in 3D spheroids.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},350029,1790122200,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nLK-1: an investigational therapy targeting hCG-β in metastatic breast, bladder, ovarian, and cervical cancers  \nJ. Helena Kinion1,2, Michael B. McAllister1, James E. Summerton1 & Brian P. Dolan2􀀍 Human chorionic gonadotropin beta (hCG-β), while primarily recognized for its role in pregnancy, has also been implicated in poor prognosis for cancer patients over the past several decades. Targeting dysregulated hCG-β production by cancer cells may prove an effective way to combat tumor growth. We propose that targeting hCG-β production using antisense phosphorodiamidate morpholinooligomers (PMO) technology could provide a precise and effective strategy for lowering hCG-β levels. This method may offer enhanced specificity and the ability to modulate hCG-β expression directly atthe mRNA transcript level. Here, we tested multiple PMO sequences targeted against hCG-β mRNA transcripts at various regions to ensure optimal sequence specificity and effective knockdown. We used cell viability assays, pregnancy test strips, and ELISA assays to determine knockdown by each PMO sequence to initially screen PMO sequences for identifying the most effective candidates. Of the sequences evaluated using ELISA, one demonstrated demonstrated effective knockdown at  \n0.5 µM and three at 1 µM. The remaining sequences required high PMO concentrations to observe a phenotype, and some did not produce measurable hCG knockdown under the conditions tested. Across nineteen PMO sequences tested in eight different cell lines, seven consistently reduced cell viability at 2-4 µM, whereas the remaining sequences showed variable or minimal effects. From the initial screen we identified the best PMO sequence, termed LK-1, for further analysis. We demonstrated that LK-1 is effective at significantly reducing hCG-β expression as measured both by western blot and ELISA assays. LK-1 treatment also showed significant reduction in cancer cell viability, reduce clonogenicity in colony formation assays, increased tumor cell death, and reduced invasion via wound healing assay in several cancer cell lines. We also showed that LK-1 is effective at reducing tumor formation in 3D spheroids. Combined, these findings suggest that targeting hCG-β production with morpholino-based therapy may represent a promising approach for cancers expressing this protein.  \nKeywords Human chorionic gonadotrophin, hCG-β, RNA therapeutics, Antisense morpholino oligomers (PMO), Cancer research, Drug discovery  \nHuman chorionic gonadotropin (hCG) is a glycoprotein hormone that plays an important role during pregnancy1. hCG is a heterodimer that consists of an alpha and beta subunit and belongs to the glycoprotein family that consists of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimlulating hormone (TSH)1. Structurally hCG exhibits extensive charge heterogeneity due to different glycosylation states1. Cole2,3 defined the five variants of hCG: hCG, hyperglycosylated hCG (H-hCG), sulfated hCG (hCG-S), β subunit hCG (hCG-β), and H-hCG-β. hCG and H-hCG are virtually always expressed in placental and other trophoblastic tumors with occasional findings in nontrophoblastic tumors1. H-hCG-β/hCG-β have been found to be expressed in numerous nontrophoblastic epithelial cancers1,4 such as bladder5–7, breast8, pancreatic9, ovarian10, cervical11–13, and many more5–9, 13–35. Its presence in tumors is often a hallmark of aggressive and metastatic disease that is associated with poor clinical outcomes1,36–40. Specifically, the expression of hCG-β has been associated with advanced tumor stage38,40–42, shorter disease-specific overall survival (OS)38, and resistances to chemotherapy and radiation treatment33,39,43,44. Several in vitro and in vivo studies have been conducted to investigate the involvement of hCG-β in cancer. These studies found that hCG-β plays a role in blocking apoptosis, promoting metastasi","cbCaicrYZR5zYUp4","https://ap.wps.com/l/cbCaicrYZR5zYUp4","pdf",5864555,18,"English","# LK-1: Investigational therapy targeting hCG-β\n## Rationale for targeting dysregulated hCG-β\n## PMO sequence screening and knockdown assessment\n## Selection of LK-1 and in vitro anti-tumor effects\n## Impact on tumor formation in 3D spheroids\n## Background: hCG structure, variants, and cancer relevance\n## hCG-β regulation and gene clusters","[{\"question\":\"Why target hCG-β in metastatic cancers?\",\"answer\":\"hCG-β is associated with aggressive, metastatic disease and poorer clinical outcomes. It has also been linked to treatment resistance and multiple cancer-promoting processes.\"},{\"question\":\"How were PMO sequences for hCG-β designed and screened?\",\"answer\":\"Researchers tested multiple PMO sequences against hCG-β mRNA transcripts across different regions. Knockdown was evaluated using cell viability assays, pregnancy test strips, and ELISA, followed by comparison of phenotype effects across concentrations.\"},{\"question\":\"What evidence supports LK-1 as the most effective candidate?\",\"answer\":\"LK-1 significantly reduced hCG-β expression measured by western blot and ELISA. It also lowered cancer cell viability, clonogenicity, increased tumor cell death, reduced invasion, and reduced tumor formation in 3D spheroids.\"}]","LK-1 - an investigational therapy targeting hCG-β in metastatic breast, bladder, ovarian, and cervical cancers | PDF",1790086824,45]