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Genetically engineered mouse models built on dual site-specific recombinase systems (dual-recombinase systems, DRS) provide new ways to model established cancers, trace and manipulate tumor components, and test functional therapy hypotheses. The article reviews how DRS enables more precise, time-resolved genetic control than single recombinase approaches, including interrogation of tumor–host interactions, the tumor microenvironment, and therapeutic responses.",{"@graph":69,"@context":123},[70,84,106],{"@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/dual-recombinase-based-mouse-models-help-decipher-cancer-biology-and-targets-for-therapy/378020/",{"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/dual-recombinase-based-mouse-models-help-decipher-cancer-biology-and-targets-for-therapy/378020.png","ImageObject",300,407,{"name":92,"@type":93},"Sophia Brooks","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are genetically engineered mouse models important for cancer research?","Question",{"text":113,"@type":114},"They help study complex biological processes by modeling molecular and cellular changes that drive malignancy, including tumor microenvironment interactions and the immune system.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What limitation exists in single recombinase systems like Cre/loxP?",{"text":118,"@type":114},"Single-step activation/inactivation makes it difficult to model sequential multistep tumorigenesis and heterogeneity, and it limits genetic validation of targets and investigation of resistance or tumor microenvironment manipulation.",{"name":120,"@type":111,"acceptedAnswer":121},"How do dual recombinase-based systems improve cancer modeling?",{"text":122,"@type":114},"They add a second controlled recombination layer, enabling independent manipulation of distinct genes and cell types at defined time points, supporting more systematic investigation of tumor ecosystems and therapeutic responses.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},378020,1791115465,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":19,"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":52},962084925636,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy  \nTina Sket1,2,3, Chiara Falcomat4, and Dieter Saur1,2,3  \n◥  \nThe advent of next-generation sequencing (NGS) and single-cell profiling technologies has revealed the complex and heterogenous ecosystem of human tumors under steady-state and therapeutic perturbation. Breakthroughs in the development of genetically engineered mouse models (GEMM) of human cancers that are based on the combination of two site-specific recombinase systems  \n[dual-recombinase system (DRS)] offer fundamental new possibilities to elucidate and understand critical drivers ofthe diverse tumor phenotypes and validate potential targets for therapy. Here, we discuss opportunities DRS-based cancer GEMMs offer to model, trace, manipulate, and functionally investigate established cancers, their interactions with the host, and their response to therapy.  \nIntroduction  \nGenetically engineered mouse models (GEMM) are crucial to study complex biological processes, such as cancer (1) . They have been invaluable in providing fundamental insights into the molecular and cellular basis of malignancies, such as the genetic and epigenetic alterations that drive tumor initiation, progression and metastatic spread to distant sites (1) . Such models have also been vital for a better understanding of the complex interactions between cancer cells and their surrounding tumor microenvironment (TME), including the immune system. They highlighted for example the importance of the tumor stroma for tumor progression, immune evasion and drug resistance. Furthermore, GEMMs have been successfully used as preclinical platforms to validate candidate therapeutic targets, test the efficacy of anticancer drugs, and elucidate mechanisms of therapy resistance (1) .  \nIn these models, tumorigenesis is typically initiated through the activation of oncogenes and/or the inactivation of tumor suppressor genes in vivo by utilizing site specific recombination (SSR) systems, such as Cre/loxP, which allows precise cell type specific tumor induction (1) . Consequently, tumors develop de novo and evolve ina native immune proficient microenvironment at the site of origin of the respective cancer type in a complex living organism. So far, several  \n1Division of Translational Cancer Research, German Cancer Research Center (DKFZ)and German Cancer Consortium(DKTK), Heidelberg, Germany. 2Chair of Translational Cancer Research and Institute of Experimental Cancer Therapy, Klinikum rechts der Isar, School of Medicine, Technische Universit€at M€unchen, Munich, Germany. 3Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany. 4Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, Gustave L. Levy Pl, New York, New York.  \nC. Falcomat and D. Saur contributed equally to this article.  \nCorresponding Authors: Chiara Falcoamat, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, GustaveL. Levy Pl, New York, NY10029 . E-mail: [chiara.falcomata@mssm.edu](chiara.falcomata@mssm.edu); and Dieter Saur, German Cancer Research Center (DKFZ) and Klinikum rechts der Isar, School of Medicine, Technische Universit€at M€unchen, Ismaninger Str. 22, Munich 81675, Germany. E-mail: [dieter.saur@tum.de](dieter.saur@tum.de)  \nCancer Res 2023;83:2279–82  \ndoi: 10.1158/0008-5472 . CAN-22-2119  \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 American Association for Cancer Research  \nGEMMs have been created that faithfully recapitulate the histologic, molecular, genetic, and clinical hallmarksoftheir human counterparts, including their inter and intratumor heterogeneity, complex stroma composition and spontaneous metastasis formation. As such, these models are indispensable for preclinical research and became","cbCaieLrCiAL35Co","https://ap.wps.com/l/cbCaieLrCiAL35Co","pdf",181730,"English","# Introduction\n# Dual Recombinase-Based Cancer Models","[{\"question\":\"Why are genetically engineered mouse models important for cancer research?\",\"answer\":\"They help study complex biological processes by modeling molecular and cellular changes that drive malignancy, including tumor microenvironment interactions and the immune system.\"},{\"question\":\"What limitation exists in single recombinase systems like Cre/loxP?\",\"answer\":\"Single-step activation/inactivation makes it difficult to model sequential multistep tumorigenesis and heterogeneity, and it limits genetic validation of targets and investigation of resistance or tumor microenvironment manipulation.\"},{\"question\":\"How do dual recombinase-based systems improve cancer modeling?\",\"answer\":\"They add a second controlled recombination layer, enabling independent manipulation of distinct genes and cell types at defined time points, supporting more systematic investigation of tumor ecosystems and therapeutic responses.\"}]","Dual Recombinase–Based Mouse Models Help Decipher Cancer Biology and Targets for Therapy | PDF",1790228044]