[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-377433-105":59,"doc-detail-377433-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","treatment-of-evolving-cancers-will-require-dynamic-decision-support","Treatment of evolving cancers will require dynamic decision support","","Cancer research has traditionally emphasized developing new agents, yet the dose and frequency of existing drugs remains underexplored. Most therapies follow predetermined schedules seeking maximum tolerated dose and adjusting mainly for toxicity. This perspective argues that cancer’s evolving complexity demands dynamic, personalized decision-making. It proposes mapping each patient to a strategy matching current disease features and treatment goals, using mathematical modeling and an ADAPT five-step paradigm integrating data across scales.",{"@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/treatment-of-evolving-cancers-will-require-dynamic-decision-support/377433/",{"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/treatment-of-evolving-cancers-will-require-dynamic-decision-support/377433.png","ImageObject",300,407,{"name":92,"@type":93},"Fans","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is the maximum tolerated dose (MTD) paradigm considered insufficient?","Question",{"text":112,"@type":113},"MTD focuses on predetermined dose escalation and toxicity adjustment, but it does not address key challenges of cancer heterogeneity and evolution. Evidence suggests that the “more is better” idea may not apply equally to targeted and immunotherapies.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What clinical trade-off does the “dose makes the poison” principle describe?",{"text":117,"@type":113},"The principle highlights that the same systemic therapy can either overcome otherwise incurable disease at the right dose or cause life-threatening toxicity or ineffective treatment at doses that are too high or too low.",{"name":119,"@type":110,"acceptedAnswer":120},"What approach does the paper propose to enable personalization of treatment schedules?",{"text":121,"@type":113},"The paper introduces mathematical modeling and an ADAPT (Adaptive Dosing Adjusted for Personalized Tumorscapes) five-step paradigm to integrate data across scales and derive dynamic, personalized scheduling strategies.","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},377433,1790660338,{"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":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"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":145},5909892330395,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Author Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \n\n| | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>Ann Oncol. Author manuscript; available in PMC 2023 November 30. |\n| --- | --- |\n\nPublished in final edited form as:  \nAnn Oncol. 2023 October ; 34(10): 867–884. doi:10.1016/j.annonc.2023.08.008 .  \nTreatment of evolving cancers will require dynamic decision support  \nM. A. R. Strobl 1,2,†, J. Gallaher1,†, M. Robertson-Tessi 1 , J. West 1,‡, A. R. A. Anderson 1,*,‡  \n1 Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa  \n2Translational Hematology and Oncology Research, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, USA  \nAbstract  \nCancer research has traditionally focused on developing new agents, but an underexplored question is that of the dose and frequency of existing drugs. Based on the modus operandi established in the early days of chemotherapies, most drugs are administered according to predetermined schedules that seek to deliver the maximum tolerated dose and are only adjusted for toxicity. However, we believe that the complex, evolving nature of cancer requires a more dynamic and personalized approach. Chronicling the milestones ofthe field, we show that the impact of schedule choice crucially depends on processes driving treatment response and failure. As such, cancer heterogeneity and evolution dictate that a one-size-fits-all solution is unlikel—dinstead, each patient should be mapped to the strategy that best matches their current disease characteristics and treatment objectives (i.e. their ‘tumorscape’) . To achieve this level of personalization, we need mathematical modeling. In this perspective, we propose a five-step‘Adaptive Dosing Adjusted for Personalized Tumorscapes (ADAPT)’ paradigm to integrate data and understanding across scales and derive dynamic and personalized schedules. We conclude with promising examples of model-guided schedule personalization and a call to action to address key outstanding challenges surrounding data collection, model development, and integration.  \nKeywords  \nmathematical modeling; treatment scheduling; cancer ecology and evolution  \nThis is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)).  \n* Correspondence to: Prof. Alexander A. R. A. Anderson, Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA. Tel: +1-813-745-6119, A†Tlexheasrut.Anhorson@mofontributedftq.ouglly(Aas. Rco. -Afi.rAstdersouthor)t.o this work.  \n‡These authors contributed equally as co-senior authors to this work.  \nDISCLOSURE  \nThe authors have declared no conflicts of interest.  \nAuthor Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \nStrobl et al. Page 2  \nINTRODUCTION  \nThe state of decision making in the clinic  \n‘The dose makes the poison’—this principle by Paracelsus, a 16th century physician and pioneer of modern Western medicine, epitomizes the inherent trade-offs of systemic cancer therapy. If given at the right dose, then anticancer agents can overcome disease incurable by surgery or radiotherapy alone; however, given at too high or too low a dose they can incur life-threatening toxicity or be ineffectual. But what is this ‘magic bullet dose’1? Current clinical practice is largely guided by the maximum tolerated dose (MTD) paradigm, which emerged from early pioneering work on chemotherapies for the treatment of leukemias.2–4 It seeks to maximize the tumor cell kill, and thus the chance of cure, by administering the highest dose which can be given before unacceptable side-effects are observed. This dose is established in phase I clinical trials, and in practice is adjusted only in the case of toxicity, interference with other treatments, insurance questions, or tumor progression.4–6  \nRapid and potentially si","cbCairbuuN8VRDNW","https://ap.wps.com/l/cbCairbuuN8VRDNW","pdf",1061219,32,"English","# Abstract\n# Introduction\n## The state of decision making in the clinic","[{\"question\":\"Why is the maximum tolerated dose (MTD) paradigm considered insufficient?\",\"answer\":\"MTD focuses on predetermined dose escalation and toxicity adjustment, but it does not address key challenges of cancer heterogeneity and evolution. Evidence suggests that the “more is better” idea may not apply equally to targeted and immunotherapies.\"},{\"question\":\"What clinical trade-off does the “dose makes the poison” principle describe?\",\"answer\":\"The principle highlights that the same systemic therapy can either overcome otherwise incurable disease at the right dose or cause life-threatening toxicity or ineffective treatment at doses that are too high or too low.\"},{\"question\":\"What approach does the paper propose to enable personalization of treatment schedules?\",\"answer\":\"The paper introduces mathematical modeling and an ADAPT (Adaptive Dosing Adjusted for Personalized Tumorscapes) five-step paradigm to integrate data across scales and derive dynamic, personalized scheduling strategies.\"}]","Treatment of evolving cancers will require dynamic decision support | PDF",1790224934,81]