[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-373395-105":59,"doc-detail-373395-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","tissue-agnostic-cancer-therapies-promise-reality-and-the-path-forward","Tissue-agnostic cancer therapies - promise, reality, and the path forward","","Tissue-agnostic cancer therapies aim to transform oncology by matching treatment to molecular drivers rather than the tissue of origin. Evidence from large-scale real-world tumor analyses shows a substantial share of molecularly profiled tumors with tissue-agnostic indications, though meaningful treatment gaps remain for eligible patients. Implementation challenges include limited molecular testing and delays in timely matching, plus systemic barriers in healthcare, regulation, and education. Clinical complexity arises from context-dependent mechanisms, resistance, and the need for combination strategies, supported by real-world evidence and ongoing trial design.",{"@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":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/tissue-agnostic-cancer-therapies-promise-reality-and-the-path-forward/373395/",{"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/tissue-agnostic-cancer-therapies-promise-reality-and-the-path-forward/373395.png","ImageObject",300,407,{"name":92,"@type":93},"Taylor Morgan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does “tissue-agnostic” therapy mean in oncology?","Question",{"text":112,"@type":113},"It means selecting cancer treatment based on molecular drivers rather than the tumor’s tissue of origin, enabling targeted action on specific biomarkers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What did the real-world analysis of nearly 300,000 tumors show?",{"text":117,"@type":113},"About 21.5% of molecularly profiled tumors had at least one tissue-agnostic indication, while 5.4% had no cancer-specific indication, with prevalence varying widely by tumor type.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is real-world adoption of tissue-agnostic treatments still limited?",{"text":121,"@type":113},"Eligible patients are often not matched promptly to the right therapy because of gaps in molecular testing, timely matching, and broader systemic issues across healthcare systems, regulations, and medical education.","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},373395,1792720125,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":19,"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":52},1099523885336,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","| Comment \u003Cbr>[https://doi.org/10.1038/s41467-025-60369-1](https://doi.org/10.1038/s41467-025-60369-1) |\n| --- |\n| Tissue-agnostic cancer therapies: promise, reality, and the path forward\u003Cbr>Vivek Subbiah  Check for updates |\n\nTissue-agnostic cancer therapies promise to revolutionize oncology by targeting molecular drivers. Sledge et al.’s study of nearly 300,000 tumors found 21.5% with tissue-agnostic indications. Despite nine FDA approvals, real-world implementation challenges persist. Progress depends on universal genomic testing, anoncogenomic-savvy workforce, innovative trials, updated regulations, and real-world evidence to maximize potential.  \nThe oncology landscape has undergone a remarkable transformation with the emergence of tissue-agnostic therapeutic approaches1. At its core, the concept—treating cancer based on molecular drivers rather than tissue of origin—is both conceptually simple and clinically transformative Pembrolizumab made history in 2017 as the first tissueagnostic therapy receiving accelerated approval for MSI-H/dMMR solid tumors in both adults and children. By 2023, it received full approval based on data from 504 patients with over 30 cancer types. The FDA has now approved nine tissue-agnostic therapies across three categories: targeted therapies (NTRK-fusions, BRAFV600E-mutations, RET-fusions), immunotherapies (MSI-H/dMMR, TMB ≥ 10 mutations/ megabase), and an antibody-drug conjugate for HER2-positive tumors (immunohistochemistry 3+ expression)1. These tissue-agnostic and in some cases age-agnostic treatments offer critical alternatives for patients with advanced solid tumors carrying specific biomarkers—providing an option when standard approaches fail2. For many patients, especially those with rare or refractory cancers, these therapies offer a promising alternative where few exist. As these approvals were based on single-arm non-randomized studies with limited patient numbers, real-world data and evidence become essential to fully comprehend their clinical impact.  \nSledge et al. have conducted an extensive real-world analysis of nearly 300,000 molecularly profiled tumors, uncovering significant potential insights into tissue-agnostic therapies3. Their findings revealed that21.5%of these tumors possess at least one tissue-agnostic indication, while 5 .4% lack any cancer-specific indication3. The prevalence of tissue-agnostic indications varies widely across different tumor types, with frequencies ranging from 0% to 87%, depending on the tissue type3. Although drawn from a single source, this study provides valuable real-world insights into these novel therapies’implementation. The team deserves commendation for compiling comprehensive data that effectively demonstrates the practical impact of these approvals.  \nThe implementation challenge- finding the needle in the haystack and threading it  \nThe analysis reveals a concerning trend: only about one-third of eligible patients with rare tumor-agnostic indications, such as NTRK fusions, are receiving the appropriate therapy—asignificant treatment gap that demands attention. Currently, there are three approved drugs(Larotrectinib, Entrectinib, and Repotrectinib) for treating NTRK fusion-positive cancers. These drugs are not only highly effective, with impressive response rates, but they are also generally better tolerated than traditional chemotherapies. Despite these advantages, their adoption in real-world settings remains disappointingly low. As a field, we face a challenge. Despite advances in comprehensive NGSto enable the detection of rare, actionable mutations, a critical gap remains: ensuring that patients are matched to appropriate targeted therapies in a timely manner. In essence, we fail to “thread the needle”(Fig. 1). Notably, even in lung cancer-the poster-child of precision oncology with ten biomarker-driven therapies—the adoption rate for molecular testing and matching in community practice hovers at around 50%, although increasing4. If this ","cbCaiouO9uaAO0DJ","https://ap.wps.com/l/cbCaiouO9uaAO0DJ","pdf",574552,"English","# Tissue-agnostic cancer therapies: promise, reality, and the path forward\n## From promise to implementation\n## Reality check: complexity of response\n## BRAF inhibition as an example of context-dependent resistance","[{\"question\":\"What does “tissue-agnostic” therapy mean in oncology?\",\"answer\":\"It means selecting cancer treatment based on molecular drivers rather than the tumor’s tissue of origin, enabling targeted action on specific biomarkers.\"},{\"question\":\"What did the real-world analysis of nearly 300,000 tumors show?\",\"answer\":\"About 21.5% of molecularly profiled tumors had at least one tissue-agnostic indication, while 5.4% had no cancer-specific indication, with prevalence varying widely by tumor type.\"},{\"question\":\"Why is real-world adoption of tissue-agnostic treatments still limited?\",\"answer\":\"Eligible patients are often not matched promptly to the right therapy because of gaps in molecular testing, timely matching, and broader systemic issues across healthcare systems, regulations, and medical education.\"}]","Tissue-agnostic cancer therapies - promise, reality, and the path forward | PDF",1790199495]