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It argues that no single modality is universally sufficient, emphasizing cross-technology integration for maximum impact and adaptive, data-driven personalized medicine.",{"@graph":14,"@context":73},[15,34,56],{"@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/innovative-strategies-to-overcome-cancer-drug-resistance-review-open-access/364050/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/innovative-strategies-to-overcome-cancer-drug-resistance-review-open-access/364050.png","ImageObject",300,407,{"name":42,"@type":43},"LangkahRina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-24","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What factors drive cancer drug resistance?","Question",{"text":63,"@type":64},"Cancer drug resistance is driven by genetic mutations, epigenetic plasticity, and interactions within the tumor microenvironment.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does this review link resistance mechanisms to treatments?",{"text":68,"@type":64},"It maps specific molecular drivers to therapeutic interventions, ranging from chemosensitizers and targeted therapies to emerging AI-guided strategies.",{"name":70,"@type":61,"acceptedAnswer":71},"Why do the authors emphasize combining modalities instead of relying on one treatment approach?",{"text":72,"@type":64},"They conclude that no single modality is universally sufficient; maximal benefit comes from strategic cross-talk between technologies, such as using AI to predict resistance evolution and optimizing combination timing.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},364050,1791331006,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Rejili etal. Discover Oncology (2026) 17:1243 Discover Oncology  \n[https://doi.org/10.1007/s12672-026-05260-1](https://doi.org/10.1007/s12672-026-05260-1)  \nREVIEW Open Access  \nInnovative strategies to overcome cancer drug resistance: from nanodelivery systems to targeted therapeutics  \nMokhtar Rejili1, Najma Farahani2, Mina Alimohammadi3 and Kiavash Hushmandi4*  \n*Correspondence:  \nKiavash Hushmandi [houshmandiK@bmsu.ac.ir](houshmandiK@bmsu.ac.ir); [Houshmandi.kia7@ut.ac.ir](Houshmandi.kia7@ut.ac.ir)[ ](Houshmandi.kia7@ut.ac.ir)1Department of Biology, College of Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia 2Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, TeMs. C, Islamic Azad University, Tehran, Iran  \n3Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran  \nAbstract  \nCancer drug resistance, driven by complex genetic mutations, epigenetic plasticity, and tumor microenvironment interactions, remains the primary cause of therapeutic failure and poor patient survival. This review critically synthesizes current resistance mechanisms to propose a unified framework that maps specific molecular drivers to corresponding therapeutic interventions, ranging from conventional chemosensitizers to emerging AI-guided strategies. We demonstrate that while chemosensitizers effectively reverse efflux-mediated resistance and that targeted therapies address specific oncogenic drivers, their efficacy is often limited by biological barriers; conversely, nanoparticle delivery systems significantly increase bioavailability, and CRISPR/Cas9 offers precise correction of intrinsic genetic defects. Crucially, we identify that no single modality is universally sufficient; instead, maximal therapeutic impact arises from the strategic cross-talk between technologies, such as the use of AI to predict resistance evolution and optimize the timing of combination therapies or nanocarrier-delivered gene editing. Future clinical success depends on shifting from isolated treatment protocols to interdisciplinary, data-driven personalized medicine that dynamically adapts to the evolving landscape of tumor resistance, ultimately transforming fatal malignancies into manageable chronic conditions.  \nKey Points  \n• Drug resistance remains a major barrier in cancer therapy, as cancer cells adapt and tolerate treatments, resulting in poorer patient outcomes.  \n• Cancer cells employ complex genetic, epigenetic, and microenvironmental mechanisms to evade drug effects and promote survival.  \n• Multidrug resistance often involves ABC transporters such as P-glycoprotein, which actively expel anticancer drugs from cells.  \n• Advances such as targeted therapies, nanotechnology-based delivery, and adaptive dosing have improved outcomes, but resistance persists.  \n• Comprehensive strategies integrating genomics, proteomics, and machine learning are also vital for overcoming cancer drug resistance.  \nKeywords Cancer drug resistance, Tumor microenvironment, Nanoparticle drug delivery, CRISPR/Cas9 gene editing, Artificial intelligence in oncology  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a ","cbCaiu7TabEr2M07","https://ap.wps.com/l/cbCaiu7TabEr2M07","pdf",6185177,54,"English","# Abstract\n# Key Points\n# 1 Introduction","[{\"question\":\"What factors drive cancer drug resistance?\",\"answer\":\"Cancer drug resistance is driven by genetic mutations, epigenetic plasticity, and interactions within the tumor microenvironment.\"},{\"question\":\"How does this review link resistance mechanisms to treatments?\",\"answer\":\"It maps specific molecular drivers to therapeutic interventions, ranging from chemosensitizers and targeted therapies to emerging AI-guided strategies.\"},{\"question\":\"Why do the authors emphasize combining modalities instead of relying on one treatment approach?\",\"answer\":\"They conclude that no single modality is universally sufficient; maximal benefit comes from strategic cross-talk between technologies, such as using AI to predict resistance evolution and optimizing combination timing.\"}]","Innovative strategies to overcome cancer drug resistance - review open access | PDF",1790155334,136]