[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-372204-105":59,"doc-detail-372204-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","mechanisms-and-strategies-to-overcome-drug-resistance-in-colorectal-cancer-review","Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer - Review","","Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide, with substantial impact on public health. Although treatments such as surgery, chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy have progressed, drug resistance continues to drive treatment failure, poor progression-free survival, and recurrence. Resistance mechanisms in CRC involve genetic mutations, epigenetic changes, tumor heterogeneity, and the tumor microenvironment. This review summarizes mechanisms and explores strategies under investigation to counteract resistance.",{"@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/mechanisms-and-strategies-to-overcome-drug-resistance-in-colorectal-cancer-review/372204/",{"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/mechanisms-and-strategies-to-overcome-drug-resistance-in-colorectal-cancer-review/372204.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is drug resistance a major problem in colorectal cancer treatment?","Question",{"text":112,"@type":113},"Despite progress in surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, resistance often causes treatment failure, poor progression-free survival, and cancer recurrence.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What mechanisms contribute to drug resistance in colorectal cancer?",{"text":117,"@type":113},"Drug resistance is multifactorial, involving genetic mutations, epigenetic alterations, tumor heterogeneity, and the tumor microenvironment.",{"name":119,"@type":110,"acceptedAnswer":120},"What resistance-targeting strategies does the review discuss?",{"text":121,"@type":113},"The review discusses strategies such as targeting drug transport, key signaling pathways, DNA damage response, cell death pathways, epigenetic modifications, cancer stem cells, and the tumor microenvironment.","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},372204,1790789316,{"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":52,"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},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Review  \nMechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer  \nJennifer Haynes * and Prasath Manogaran  \nAcademic Editor: Carmine Stolfi  \nReceived: 10 January 2025  \nRevised: 22 February 2025  \nAccepted: 24 February 2025  \nPublished: 25 February 2025  \nCitation: Haynes, J.; Manogaran, P. Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer. Int. J. Mol. Sci. 2025, 26, 1988. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms26051988  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \nDepartment of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA; [prasathmanogaran@gmail.com](prasathmanogaran@gmail.com)  \n* [Correspondence: haynesje@marshall.edu](Correspondence: haynesje@marshall.edu); Tel.: +1-304-696-7335  \nAbstract: Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide, with a significant impact on public health. Current treatment options include surgery, chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy. Despite advancements in these therapeutic modalities, resistance remains a significant challenge, often leading to treatment failure, poor progression-free survival, and cancer recurrence. Mechanisms of resistance in CRC are multifaceted, involving genetic mutations, epigenetic alterations, tumor heterogeneity, and the tumor microenvironment. Understanding these mechanisms at the molecular level is crucial for identifying novel therapeutic targets and developing strategies to overcome resistance. This review provides an overview of the diverse mechanisms driving drug resistance in sporadic CRC and discusses strategies currently under investigation to counteract this resistance. Several promising strategies are being explored, including targeting drug transport, key signaling pathways, DNA damage response, cell death pathways, epigenetic modifications, cancer stem cells, and the tumor microenvironment. The integration of emerging therapeutic approaches that target resistance mechanisms aims to enhance the efficacy of current CRC treatments and improve patient outcomes.  \nKeywords: colorectal cancer; drug resistance; chemotherapy; targeted therapy; immunotherapy; resistance mechanisms; therapeutic strategies  \n1. Introduction  \n1.1. Colorectal Cancer Incidence and Risk Factors  \nColorectal cancer (CRC) is a disease that includes both colon cancer and rectal cancer, often grouped together because they have many common features. The incidence rates for CRC in the United States from 2016 to 2020 were 35.3 per 100,000 people, with 40.7 in 100,000 for men and 30.6 per 100,000 for women [1] . While CRC incidence rates have gone down overall since their peak in 1985, the prevalence of CRC has been rising in younger adults (20–49 years) for decades [2] . The median age of diagnosis for CRC is 67; however, younger patients tend to present with a more advanced-stage disease compared to older patients [3] . In the United States and worldwide, CRC is the third most common cancer diagnosed in both men and women, and the second leading cause of cancer-related deaths when numbers for men and women are combined [1,4] . CRC is particularly deadly because it can grow undetected without causing symptoms for many years and may not cause significant health problems until the tumor is large or at an advanced stage and may have spread to other parts of the body.  \nThere are many factors that can increase the risk for CRC, including both nonmodifiable biological risk factors and modifiable lifestyle risk factors [5] . Biological or  \ngenetic f","cbCaingCA2K1oACj","https://ap.wps.com/l/cbCaingCA2K1oACj","pdf",2975136,35,"English","# Introduction\n## Colorectal Cancer Incidence and Risk Factors\n## Colorectal Cancer Pathogenesis","[{\"question\":\"Why is drug resistance a major problem in colorectal cancer treatment?\",\"answer\":\"Despite progress in surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, resistance often causes treatment failure, poor progression-free survival, and cancer recurrence.\"},{\"question\":\"What mechanisms contribute to drug resistance in colorectal cancer?\",\"answer\":\"Drug resistance is multifactorial, involving genetic mutations, epigenetic alterations, tumor heterogeneity, and the tumor microenvironment.\"},{\"question\":\"What resistance-targeting strategies does the review discuss?\",\"answer\":\"The review discusses strategies such as targeting drug transport, key signaling pathways, DNA damage response, cell death pathways, epigenetic modifications, cancer stem cells, and the tumor microenvironment.\"}]","Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer - Review | PDF",1790193972,88]