[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-377061-105":3,"detail-sidebar-cat-0-en-105":79,"doc-detail-377061-en":129},{"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":72,"head_meta":74,"extra_data":76,"updated_unix":78},105,"en","tumor-agnostic-precision-medicine-from-the-aacr-genie-database-clinical-implications","Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications","","Tumor-agnostic precision medicine is shaped by biomarker-driven therapies that extend beyond tissue-of-origin and enable pan-cancer responses. The study uses AACR GENIE data (version 13.0) to map the clinicogenomic landscape of approved alterations, including BRAFV600E mutations, RET fusions, NTRK fusions, high tumor mutation burden (TMB), and dMMR/MSI-High. Among 168,423 sequenced samples, key targets show measurable prevalences, while the article summarizes biological context and supporting evidence for therapies such as pembrolizumab, dostarlimab, larotrectinib, entrectinib, selpercatinib, and dabrafenib/trametinib.",{"@graph":14,"@context":71},[15,34,54],{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/tumor-agnostic-precision-medicine-from-the-aacr-genie-database-clinical-implications/377061/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":48,"encodingFormat":47,"isAccessibleForFree":49,"interactionStatistic":50},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/tumor-agnostic-precision-medicine-from-the-aacr-genie-database-clinical-implications/377061.png","ImageObject",300,407,{"name":42,"@type":43},"Angel","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":51,"interactionType":52,"userInteractionCount":26},"InteractionCounter",{"@type":53},"ViewAction",{"@type":55,"mainEntity":56},"FAQPage",[57,63,67],{"name":58,"@type":59,"acceptedAnswer":60},"What is the main purpose of using the AACR GENIE database in this work?","Question",{"text":61,"@type":62},"To explore the clinicogenomic landscape and distribution of tissue-agnostic alterations across many cancer types using GENIE sequencing data.","Answer",{"name":64,"@type":59,"acceptedAnswer":65},"Which molecular biomarkers are discussed as having FDA tissue-agnostic approvals?",{"text":66,"@type":62},"BRAFV600E mutations, RET fusions, NTRK fusions, high tumor mutation burden (TMB), and dMMR/high microsatellite instability (MSI-High) cancers.",{"name":68,"@type":59,"acceptedAnswer":69},"What therapies are highlighted as relevant to these tissue-agnostic targets?",{"text":70,"@type":62},"The article summarizes evidence for approved drugs including pembrolizumab, dostarlimab, larotrectinib, entrectinib, selpercatinib, and dabrafenib/trametinib combinations.","https://schema.org",{"og:url":32,"og:type":73,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":75,"canonical":32},"index,follow",{"doc_id":77,"site_id":7},377061,1790269342,{"code":4,"msg":80,"data":81},"success",[82,86,90,94,99,104,108,113,118,121,125],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":83,"show_sort_weight":84,"slug":85},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":87,"show_sort_weight":88,"slug":89},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":91,"show_sort_weight":92,"slug":93},"Exam",70,"exam",{"id":95,"doc_module":4,"doc_module_name":25,"category_name":96,"show_sort_weight":97,"slug":98},5,"Comic",60,"comic",{"id":100,"doc_module":4,"doc_module_name":25,"category_name":101,"show_sort_weight":102,"slug":103},6,"Technology",50,"technology",{"id":105,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":106,"slug":107},7,40,"healthcare",{"id":109,"doc_module":4,"doc_module_name":25,"category_name":110,"show_sort_weight":111,"slug":112},8,"Research & Report",30,"research-report",{"id":114,"doc_module":4,"doc_module_name":25,"category_name":115,"show_sort_weight":116,"slug":117},9,"Religion & Spirituality",20,"religion-spirituality",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":119,"show_sort_weight":116,"slug":120},"World Cup","world-cup",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":123,"show_sort_weight":122,"slug":124},10,"Lifestyle","lifestyle",{"id":126,"doc_module":4,"doc_module_name":25,"category_name":127,"show_sort_weight":95,"slug":128},19,"General","general",{"code":4,"msg":80,"data":130},{"doc_id":77,"user_id":131,"nickname":42,"user_avatar":132,"doc_module":4,"category_id":105,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":109,"language":138,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":139,"faqs":140,"seo_title":141,"seo_description":12,"update_tm":142,"read_time":116},687207412472,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications  \nMohamed A. Gouda1, Blessie E. Nelson1, Lars Buschhorn2, Adam Wahida2, and Vivek Subbiah1,3,4  \n◥  \nBiomarker-driven cancer therapy has revolutionized precision oncology. With a better understanding of tumor biology, tissueagnostic targets have been characterized and explored, which ultimately led to therapeutics with pan-cancer efficacy. To date,five molecular biomarkers have obtained FDA tissue-agnostic approval for targeted therapies and immunotherapies. Those include BRAFV600E mutations, RET fusions, NTRK fusions, high tumor mutation burden (TMB), and deficient mismatch repair/ high microsatellite instability (dMMR/MSI-High) . Herein, we have used data from AACR project GENIE to explore the clinicogenomic landscape of these alterations. AACR GENIE is a publicly  \naccessible registry of genomic data from multiple collaborating cancer centers. Current database (version 13.0) includes sequencing data of 168,423 samples collected from patients with different cancers. We were able to identify BRAFV600E, RET fusions, NTRK fusions, and high TMBin2.9%,1.6%,1.5%, and15.2%ofpan-cancer samples, respectively. In this article, we describe the distribution of those tissue-agnostic targets among different cancer types. In addition, we summarize the current prospect on the biology of these alterations and evidence on approved drugs, including pembrolizumab, dostarilmab, larotrectinib, entrectinib, selpercatinib, and dabrafenib/trametinib combination.  \nIntroduction  \nFor decades, cancer management has relied primarily on microscopic examination of tumor tissue with focus on understanding its exact pathology, including the extent of infiltration and the tissue of origin (1) . Tumors have been, therefore, managed according to their location in the human body and management guidelines have made this distinction clear by being developed in a site-specific approach. Moreover, cancer research, cancer clinical trials, and anticancer drugs were all developed on the basis of histology and site. However, with the rapid evolution that happened in clinical genomic testing and contemporaneous advances in the development of precision cancer therapies, genomically targeted therapies and agents that arm the immune system have been introduced.  \nThe list of targeted therapies, that act on specific molecular alterations, has exponentially grown in the past decade (2) . Moreover, the introduction of immunotherapy has brought cancer therapeutics to the next level by enabling the patients’ body itself to fight cancer (3) . That being said, beyond the era of site-specific cancer management, tissue-agnostic biomarkers across different cancer histologies have emerged. This was mainly driven by actionable alterationsidentified by next-generation sequencing (NGS) and the availability of medicines  \n1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2Division of Gynecological Oncology, National Center for Tumor Diseases (NCT), Heidelberg, Germany. 3Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 4MD Anderson Cancer Network, The University of Texas MD Anderson Cancer Center, Houston, Texas.  \nCorresponding Author: Vivek Subbiah, Division of Cancer Medicine, Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe  \nBoulevard, Houston, TX 77030 . E-mail: [vsubbiah@mdanderson.org](vsubbiah@mdanderson.org)  \n[Clin Cancer Res 2023](Clin Cancer Res 2023);[29:2753](29:2753)–[60](60)  \n[doi:](doi: 10.1158/1078-0432.CCR-23-0090)[ 10.1158/1078-0432.CCR-23-0090](doi: 10.1158/1078-0432.CCR-23-0090)  \nThis open access article is distributed under the Creative Commons AttributionNonCommercial-NoDerivatives 4 . 0 International (CC BY-NC-ND 4 . 0) license.  \n􀀁2023The Authors;Published by the Am","cbCaifcncTugUtkq","https://ap.wps.com/l/cbCaifcncTugUtkq","pdf",2079209,"English","# Introduction\n# Molecular Biomarkers and Targets in Tissue-Agnostic Approvals\n## BRAFV600E Mutations","[{\"question\":\"What is the main purpose of using the AACR GENIE database in this work?\",\"answer\":\"To explore the clinicogenomic landscape and distribution of tissue-agnostic alterations across many cancer types using GENIE sequencing data.\"},{\"question\":\"Which molecular biomarkers are discussed as having FDA tissue-agnostic approvals?\",\"answer\":\"BRAFV600E mutations, RET fusions, NTRK fusions, high tumor mutation burden (TMB), and dMMR/high microsatellite instability (MSI-High) cancers.\"},{\"question\":\"What therapies are highlighted as relevant to these tissue-agnostic targets?\",\"answer\":\"The article summarizes evidence for approved drugs including pembrolizumab, dostarlimab, larotrectinib, entrectinib, selpercatinib, and dabrafenib/trametinib combinations.\"}]","Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications | PDF",1790222923]