[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332101-105":59,"doc-detail-332101-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","the-prognostic-value-of-mek-pathwayassociated-estrogen-receptor-signaling-activity-for-female-cancers","The prognostic value of MEK pathway–associated estrogen receptor signaling activity for female cancers","","Endocrine therapy is not reliably effective for gynecologic cancers beyond breast cancer, and resistance in estrogen receptor–positive tumors remains poorly explained. This retrospective study evaluates estrogen receptor (ER) signaling pathway activities across breast, ovarian, endometrial, and cervical cancers to determine predictors of endocrine therapy responsiveness. Clinical and genomic cohorts were analyzed using cBioPortal, with ESR1 expression and pathway enrichment scoring to stratify patients by low/high signatures. Findings identify combined ESR1 and estrogen response signaling as a breast cancer prognostic indicator and reveal ER–MEK cross-regulation, defining MEK downstream genes as potential biomarkers.",{"@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/the-prognostic-value-of-mek-pathwayassociated-estrogen-receptor-signaling-activity-for-female-cancers/332101/",{"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/the-prognostic-value-of-mek-pathwayassociated-estrogen-receptor-signaling-activity-for-female-cancers/332101.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is endocrine therapy resistance in estrogen receptor positive gynecologic cancers important to study?","Question",{"text":112,"@type":113},"Endocrine therapy is less effective for gynecologic cancers other than breast cancer, and the mechanisms of resistance in estrogen receptor positive disease are still poorly understood.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were patients grouped in the study?",{"text":117,"@type":113},"Patients were classified into four groups using ESR1 expression level together with sample-level pathway enrichment scores (EERES), representing low/high ESR1 and low/high EERES.",{"name":119,"@type":110,"acceptedAnswer":120},"What key prognostic and biomarker findings were reported?",{"text":121,"@type":113},"A combined prognostic value of ESR1 expression and corresponding estrogen response signaling (EERES score) was identified for breast cancer, and ER signaling was found to cross-regulate MEK pathway activation, with several MEK downstream genes proposed as endocrine therapy response biomarkers.","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},332101,1790908273,{"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":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"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":143,"read_time":144,"preview_page_count":4},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","British Journal of Cancer [www.nature.com/bjc](www.nature.com/bjc)  \nARTICLE OPEN   \nTranslational Therapeutics  \nThe prognostic value of MEK pathway–associated estrogen receptor signaling activity for female cancers  \nChun Wai Ng 1, Yvonne T. M. Tsang 1, David M. Gershenson1 and Kwong-Kwok Wong 1 ✉  \n© The Author(s) 2024  \n|  |  |  |\n| --- | --- | --- |\n|  | BACKGROUND: Other than for breast cancer, endocrine therapy has not been highly effective for gynecologic cancers. Endocrine therapy resistance in estrogen receptor positive gynecologic cancers is still poorly understood. In this retrospective study, we examined the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify those that may predict endocrine therapy responsiveness.\u003Cbr>METHODS: Clinical and genomic data of women with breast and gynecological cancers were downloaded from cBioPortal for Cancer Genomics. Estrogen receptor alpha (ESR1) expression level and sample-level pathway enrichment scores (EERES) were calculated to classify patients into four groups (low/high ESR1 and low/high EERES) . Correlation between ESR1/EERES score and survival was further validated with RNAseq data from low-grade serous ovarian cancer. Pathway analyses were performed among different ESR1/EERES groups to identify genes that correlate with endocrine resistance, which are validated using Cancer Cell Line Encyclopedia gene expression and Genomics of Drug Sensitivity in Cancer data.\u003Cbr>RESULTS: We identified a novel combined prognostic value of ESR1 expression and the corresponding estrogen response signaling (EERES score) for breast cancer. The combined prognostic value (ESR1/EERES) may be applicable to other gynecologic cancers. More importantly, we discovered that ER signaling can cross-regulate MEK pathway activation. We identified downstream genes in the MEK pathway (EPHA2, INAVA, MALL, MPZL2, PCDH1, and TNFRSF21) that are potential endocrine therapy response biomarkers. CONCLUSION: This study demonstrated that targeting both the ER and the ER signaling activity related MEK pathway may aid the |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| development of endocrine therapy strategies for personalized medicine. |  |  |\n|  | British Journal of Cancer (2024) 130:1875–1884; [https://doi.org/10.1038/s41416-024-02668-w](https://doi.org/10.1038/s41416-024-02668-w) |  |\n|  |  |  |\n\nINTRODUCTION  \nEstrogen and estrogen receptor (ER) signaling pathways are involved in the development of female cancers [1–6] . Deregulated ER expression and ER signaling can lead to uncontrolled cell proliferation and cancer progression. During tumorigenesis, normal ER signaling functions to support benign cell differentiation and development are reprogrammed to support tumor cell proliferation [7, 8] . Endocrine therapy targeting this signaling pathway by blocking the activity of ERα has long been an option for the treatment of female cancers [9, 10] . The three main categories of hormonal therapeutics are selective ER modulators, aromatase inhibitors, and selective ER degraders. These ERα -targeting pharmaceutical agents are effective in treating ERα -positive breast cancer. Specifically, they can slow the growth of or shrink breast tumors and reduce the risk of recurrence after surgery [11] . Although gynecologic cancers have long been recognized to be caused by abnormal estrogen pathway activity, the effectiveness of endocrine therapy for gynecologic cancers other than breast cancer is still controversial, and biomarkers for precision treatment of them are needed [12] .  \nIn a retrospective study, hormonal maintenance therapy resulted in a lower risk of progression in patients with stage II-IV  \nlow-grade ovarian serous carcinoma than in patients who underwent observation only but did not result in a significant difference in overall survival","cbCailb92qnQ0QUG","https://ap.wps.com/l/cbCailb92qnQ0QUG","pdf",1893880,"English","# Background\n# Methods\n# Results\n# Conclusion","[{\"question\":\"Why is endocrine therapy resistance in estrogen receptor positive gynecologic cancers important to study?\",\"answer\":\"Endocrine therapy is less effective for gynecologic cancers other than breast cancer, and the mechanisms of resistance in estrogen receptor positive disease are still poorly understood.\"},{\"question\":\"How were patients grouped in the study?\",\"answer\":\"Patients were classified into four groups using ESR1 expression level together with sample-level pathway enrichment scores (EERES), representing low/high ESR1 and low/high EERES.\"},{\"question\":\"What key prognostic and biomarker findings were reported?\",\"answer\":\"A combined prognostic value of ESR1 expression and corresponding estrogen response signaling (EERES score) was identified for breast cancer, and ER signaling was found to cross-regulate MEK pathway activation, with several MEK downstream genes proposed as endocrine therapy response biomarkers.\"}]","The prognostic value of MEK pathway–associated estrogen receptor signaling activity for female cancers | PDF",1789996787,25]