[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-380125-105":59,"doc-detail-380125-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","a-landscape-of-response-to-drug-combinations-in-non-small-cell-lung-cancer-article","A landscape of response to drug combinations in non-small cell lung cancer - Article","","Drug combinations are used to overcome limited efficacy of single agents, yet designing and testing them remains challenging. This study reports a uniquely large dataset screening over 5000 targeted agent combinations across 81 non-small cell lung cancer cell lines. Results show profound heterogeneity of response across tumor models and that strong efficacy gains over single agents are rare. Activity gains more often occur when co-targeting functionally proximal genes, suggesting context-specific, tumor-restricted strategies. The resource includes additional validation to support efficient combination design and training for synergy prediction.",{"@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/a-landscape-of-response-to-drug-combinations-in-non-small-cell-lung-cancer-article/380125/",{"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/a-landscape-of-response-to-drug-combinations-in-non-small-cell-lung-cancer-article/380125.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How large is the dataset used to study drug combinations in non-small cell lung cancer?","Question",{"text":112,"@type":113},"The dataset screens over 5000 targeted agent combinations across 81 non-small cell lung cancer cell lines.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What does the analysis show about response across tumor models?",{"text":117,"@type":113},"Response is profoundly heterogeneous across the tumor models, and strong efficacy gains over single agents are very rare.",{"name":119,"@type":110,"acceptedAnswer":120},"When are activity gains over single agents more likely to occur?",{"text":121,"@type":113},"Activity gains are more often seen when co-targeting functionally proximal genes, offering a strategy for designing more efficient combinations.","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},380125,1792164721,{"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":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"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},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Article [https://doi.org/10.1038/s41467-023-39528-9](https://doi.org/10.1038/s41467-023-39528-9)  \nA landscape of response to drug  \ncombinations in non-small cell lung cancer  \nReceived: 31 January 2023  \n\n| Accepted: 14 June 2023 |\n| --- |\n| |\n| Check for updates |\n\nNishanth Ulhas Nair 1, Patricia Greninger 2, Xiaohu Zhang3,  \nAdam A. Friedman2, Arnaud Amzallag2, Eliane Cortez2, Avinash Das Sahu4, Joo Sang Lee 5, Anahita Dastur2, Regina K. Egan2, Ellen Murchie2,  \nMichele Ceribelli3, Giovanna S. Crowther2, Erin Beck3, Joseph McClanaghan2, Carleen Klump-Thomas 3, Jessica L. Boisvert2, Leah J. Damon2,  \nKelli M. Wilson 3, Jeffrey Ho2, Angela Tam2, Crystal McKnight3, Sam Michael3, Zina Itkin3, Mathew J. Garnett 6, Jeffrey A. Engelman2, Daniel A. Haber 2,3, Craig J. Thomas 7,8,9, Eytan Ruppin 1,9  & Cyril H. Benes 2,9   \nCombination of anti-cancer drugs is broadly seen as way to overcome the often-limited efficacy of single agents. The design and testing of combinations are however very challenging. Here we present a uniquely large dataset screening over 5000 targeted agent combinations across 81 non-small cell lung cancer cell lines. Our analysis reveals a profound heterogeneity of response across the tumor models. Notably, combinations very rarely result ina strong gain in efficacy over the range of response observable with single agents. Importantly, gain of activity over single agents is more often seen when co-targeting functionally proximal genes, offering a strategy for designing more efficient combinations. Because combinatorial effect is strongly contextspecific, tumor specificity should be achievable. The resource provided, together with an additional validation screen sheds light on major challengesand opportunities in building efficacious combinations against cancer and provides an opportunity for training computational models for synergy prediction.  \nModern therapeutic approaches to numerous pathologies include the use of drug combinations to obtain better efficacy and lower systemic toxicity in patients. Combinations of drugs have been frequently used to treat microorganisms infections1,2 and most notably, tri-therapy against HIV infection can yield very long lasting disease control3. Drug combinations are also frequently part of anti-cancer treatment, based mainly on empirical clinical discovery for decades4,5. Rationally  \ndesigned targeted agents have now been approved across a variety of cancers but the vast majority of patients are still treated first with combinations of “classic” genotoxic chemotherapeutic agents such as DNA damaging agents or other agents targeting cycling cells (taxanes). Targeted agents are sometimes combined with traditional cytotoxics: e.g., the targeted agent trastuzumab (an antibody against HER2) is combined with taxane to achieve higher benefit in HER2 breast  \n1Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 2Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 3Howard Hughes Medical Institute, Bethesda, MD, USA. 4University of New Mexico, Comprehensive Cancer Center, Albuquerque, NM, USA. 5Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea. 6Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK. 7Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institute of Health, Rockville, MD 20850, USA. 8Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 9These authors contributed equally: Craig J. Thomas, Eytan Ruppin, Cyril H.  \nBenes. e-mail: [eytan.ruppin@nih.gov](eytan.ruppin@nih.gov); [cyrilbenes@gmail.com](cyrilbenes@gmail.com)  \ncancer6,7. Currently, there are only few combinations involving exclusively rationally designed targeted agents that are used to treat cancer. Th","cbCaiomM8sPNuIY8","https://ap.wps.com/l/cbCaiomM8sPNuIY8","pdf",5032852,"English","# Combination efficacy and dataset scope\n## Targeted screening across NSCLC cell lines\n## Response heterogeneity and rarity of strong gains\n# Strategies for designing more efficient combinations\n## Co-targeting functionally proximal genes\n## Context-specific, tumor-specific opportunities\n# Translational relevance and challenges","[{\"question\":\"How large is the dataset used to study drug combinations in non-small cell lung cancer?\",\"answer\":\"The dataset screens over 5000 targeted agent combinations across 81 non-small cell lung cancer cell lines.\"},{\"question\":\"What does the analysis show about response across tumor models?\",\"answer\":\"Response is profoundly heterogeneous across the tumor models, and strong efficacy gains over single agents are very rare.\"},{\"question\":\"When are activity gains over single agents more likely to occur?\",\"answer\":\"Activity gains are more often seen when co-targeting functionally proximal genes, offering a strategy for designing more efficient combinations.\"}]","A landscape of response to drug combinations in non-small cell lung cancer - Article | PDF",1790238834,48]