[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-330242-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-330242-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","erk-pathway-agonism-for-cancer-therapy-evidence-insights-and-a-target-discovery-framework","ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework","","At least 40% of human cancers involve aberrant ERK pathway activity (ERKp), yet the vulnerability created by strong ERKp hyperactivation remains less explored. This review evaluates evidence that highly elevated ERKp activity can selectively harm human cancer cells across different biological backgrounds. It integrates proposed strategies to exploit ERK-associated susceptibilities into therapeutic concepts, aligns them with established pharmacological target models, and summarizes preclinical findings on ERK pathway agonism for diverse cancer settings.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/erk-pathway-agonism-for-cancer-therapy-evidence-insights-and-a-target-discovery-framework/330242/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/erk-pathway-agonism-for-cancer-therapy-evidence-insights-and-a-target-discovery-framework/330242.png","ImageObject",300,407,{"name":42,"@type":43},"Finn","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-24","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is ERK pathway activity important in cancer therapy?","Question",{"text":63,"@type":64},"At least 40% of human cancers show aberrant ERK pathway activity (ERKp). This makes ERKp a relevant axis for developing therapeutic approaches.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What does the review focus on regarding ERKp hyperactivation?",{"text":68,"@type":64},"It examines evidence for selective lethality when ERKp activity is highly elevated in human cancer cells with different backgrounds.",{"name":70,"@type":61,"acceptedAnswer":71},"How does the review propose to discover new targets for ERKp agonism?",{"text":72,"@type":64},"It presents a conceptual target-discovery framework that emphasizes leveraging mutual exclusivity among oncogenes to develop novel targeted therapies for precision oncology.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},330242,1790854153,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":55,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":108,"preview_page_count":4},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","npj | precision oncology Review article  \n\n| Published in partnership with The Hormel Institute, University of Minnesota |  | |\n| --- | --- | --- |\n| [https://doi.org/10.1038/s41698-024-00554-5](https://doi.org/10.1038/s41698-024-00554-5) |  |  |\n| ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework\u003Cbr> Check for updates |  |  |\n| Oleg Timofeev1, Philippe Giron2, Steffen Lawo 3, Martin Pichler4 & Maxim Noeparast 4  |  |  |\n| At least 40% of human cancers are associated with aberrant ERK pathway activity (ERKp) . Inhibitors targeting various effectors within the ERKp have been developed and explored for over two decades. Conversely, a substantial body of evidence suggests that both normal human cells and, notably to a greater extent, cancer cells exhibit susceptibility to hyperactivation of ERKp. However, this vulnerability of cancer cells remains relatively unexplored. In this review, wereexamine the evidence on the selective lethality of highly elevated ERKp activity in human cancer cells of varying backgrounds. We synthesize the insights proposed for harnessing this vulnerability of ERK-associated cancers for therapeutical approaches and contextualize these insights within established pharmacological cancer-targeting models. Moreover, we compile the intriguing preclinical findings of ERK pathway agonism in diverse cancer models. Lastly, we present a conceptual framework for target discovery regarding ERKp agonism, emphasizing the utilization of mutual exclusivity among oncogenes to develop novel targeted therapies for precision oncology. |  |  |\n| Background\u003Cbr>Cancer targeting: from chemotherapy to precision oncology In 1904, after a series of studies on different model organisms, Paul Erlich, a highly meritorious German medical scientist, coined chemotherapy to address his approach when chemicals were used to target infectious diseases1,2 (see Fig. 1) . Ehrlich humbly stated: Indeed, from the very origin of the art of healing, chemotherapy has existed since almost all the medicaments we employ are chemicals1. However, Ehrlich’s concept of chemotherapy unprecedently linked the chemical structure and chemoreceptors on the target cells to make sense of the pharmacological activity3,4. Headdressed chemicals that selectively exert their detrimental effect on the target cells (e.g., parasites) and not on the treated organism cells as Zauberkugeln or magic bullets1,2. Erlich had tested compounds, such as alkylating agents, to target cancer, which, in his hands, showed limited effects, far from being considered Zauberkugeln. Still, Ehrlich remained optimistic that effective chemotherapeutics could be explored in the future1. He explained this lack of effect by the high similarity between cancer and non-cancer cells1. | During World War II, in a mouse xenograft lymphoma model, two American pharmacologists, Alfred Gilman, and Louis Goodman, showed that nitrogen mustard, a warfare gas, had (chemo)therapeutic effects5,6. Their work immediately justified the treatment of a non–Hodgkin’s lymphoma patient and other cancers with nitrogen mustard5,7. Despite further knowledge about its limited efficacy and proneness to resistance, nitrogen mustard’s ephemerous success laid the foundation for establishing cancer chemotherapy as a valid field. Since then, several cancer chemotherapeutics such as Alkylating, Antimicrotubular agents, and Antimetaboliteshave been developed8. Cancer chemotherapy is a term whose definition was progressively elucidated long after it was coined, considering the expanding knowledge about chemotherapeutics’ mechanism of action and limitations. Compared to more selective therapeutics, Chemotherapeutics are considered one-size-fits-all treatments targeting different cancer types carrying distinct driveroncogenes8. Despite their narrow therapeutic window and the possibility of targeting non-cancerous dividing cells, chemotherapeuticshave saved lives in some cancer populations, such as ","cbCaioH7otXvJFJi","https://ap.wps.com/l/cbCaioH7otXvJFJi","pdf",2171884,16,"English","# Background\n## Cancer targeting: from chemotherapy to precision oncology\n## Conceptual shift toward targeted therapies\n# Selective lethality of hyperactivated ERKp\n## Evidence across diverse cancer models\n# Target discovery framework\n## Using oncogene mutual exclusivity for precision oncology","[{\"question\":\"Why is ERK pathway activity important in cancer therapy?\",\"answer\":\"At least 40% of human cancers show aberrant ERK pathway activity (ERKp). This makes ERKp a relevant axis for developing therapeutic approaches.\"},{\"question\":\"What does the review focus on regarding ERKp hyperactivation?\",\"answer\":\"It examines evidence for selective lethality when ERKp activity is highly elevated in human cancer cells with different backgrounds.\"},{\"question\":\"How does the review propose to discover new targets for ERKp agonism?\",\"answer\":\"It presents a conceptual target-discovery framework that emphasizes leveraging mutual exclusivity among oncogenes to develop novel targeted therapies for precision oncology.\"}]","ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework | PDF",1789987868]