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The review emphasizes self-organization, describing reciprocal shaping between tumor cells and their microenvironment that drives progression and resistance. It discusses how interactions within the TME can uncover prognostic markers and therapeutic targets, including extracellular matrix components, immune cells, and cytokine signaling pathways, and reports evidence that disrupting TME self-organization may improve outcomes.",{"@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/the-role-of-tumor-microenvironment-and-self-organization-in-cancer-progression-key-insights-for-therapeutic-development/340790/",{"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/the-role-of-tumor-microenvironment-and-self-organization-in-cancer-progression-key-insights-for-therapeutic-development/340790.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does the tumor microenvironment (TME) play in cancer progression?","Question",{"text":112,"@type":113},"The TME drives tumor initiation, growth, invasion, metastasis, angiogenesis, immune evasion, and therapeutic resistance through interactions among extracellular matrix components, cancer cells, non-cancer cells, and soluble factors.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does self-organization in the TME contribute to therapy resistance?",{"text":117,"@type":113},"Self-organization involves reciprocal interactions between tumor cells and their microenvironment, forming complex structures that support tumor survival and contribute to resistance against anticancer therapies.",{"name":119,"@type":110,"acceptedAnswer":120},"Which therapeutic directions are highlighted by the review?",{"text":121,"@type":113},"Targeting extracellular matrix (ECM) components and immune cells within the TME, and focusing on molecules involved in TME self-organization, are proposed to improve treatment effectiveness and help defeat drug resistance.","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},340790,1790916203,{"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":39,"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},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","The role of tumor microenvironment and self-organization in cancer progression: Key insights for therapeutic development  \nMilad Asadi1 ID , Venus Zafari1, Sanam Sadeghi-Mohammadi2, Dariush Shanehbandi3, Ufuk Mert4, Zahra Soleimani2, Ayşe Caner1* ID , Habib Zarredar2* ID  \n1Department of Basic Oncology, Ege University, Institute of Health Sciences, Izmir, Turkey 2Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 3Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran  \n4Institute of Health Sciences, Department of Basic Oncology, Ege University, Izmir, Turkey  \nArticle Info  \nArticle Type:  \nReview  \nArticle History:  \nReceived: 1 Sep. 2024  \nRevised: 8 Oct. 2024  \nAccepted: 20 Nov. 2024  \nePublished: 7 Dec. 2024  \nKeywords:  \nTumor microenvironment Self-organization Extracellular matrix Metastasis  \nInvasion  \nAbstract  \nIntroduction: The tumor  \nmicroenvironment (TME) plays a pivotal role in cancer progression, influencing tumor initiation, growth, invasion, metastasis, and response to therapies. This study explores the dynamic interactions within the TME, particularly focusing on selforganization—a process by which tumor cells and their microenvironment reciprocally shape one another, leading to cancer progression and resistance. Understanding these interactions can  \nreveal new prognostic markers and therapeutic targets within the TME, such as extracellular matrix (ECM) components, immune cells, and cytokine signaling pathways.  \nMethods: A comprehensive search method was employed to investigate the current academic literature on TME, particularly focusing on self-organization in the context of cancer progression and resistance across the PubMed, Google Scholar, and Science Direct databases.  \nResults: Recent studies suggest that therapies that disrupt TME self-organization could improve patient outcomes by defeating drug resistance and increasing the effectiveness of conventional therapy. Additionally, this research highlights the essential of understanding the biophysical properties of the TME, like cytoskeletal alterations, in the development of more effective malignancy therapy.  \nConclusion: This review indicated that targeting the ECM and immune cells within the TME can improve therapy effectiveness. Also, by focusing on TME self-organization, we can recognize new therapeutic plans to defeat drug resistance.  \nIntroduction  \nCancer, a leading cause of mortality worldwide, manifests through aberrant cellular behaviors such as uncontrolled growth, invasion, and metastasis. Conventional treatments, like surgery, chemotherapy, and radiotherapy, though widely used, often face limitations including drug resistance and adverse effects, resulting in low curative outcomes. Recent studies have highlighted the essential role of the tumor microenvironment (TME) a complex network of extracellular matrix components (ECM), cancer cells, non-cancer cells, and soluble factors, in  \ndriving tumor development. TME not only supports cancer progression and growth but also plays a critical role in angiogenesis, tumor cell migration, immune evasion, and therapeutic resistance.1-3  \nThe unique biochemical compositions of the TME, influenced by factors such as oxygen levels, pH, and fluid flux, creates an environment conducive to cancer cell survival, immune evasion, and resistance to anticancer therapies.4-7 Additionally, dysregulation of cellular pH within the tumor and the presence of an acidic microenvironment promote migration, invasion, and  \n*Corresponding authors: Habib Zarredar, Email: habib_zarredar@yahoo.com and Ayşe Caner, Emails: [ayse.caner@ege.edu.tr](ayse.caner@ege.edu.tr), ayecaner@ [gmail.com](gmail.com)  \n © 2025 The Author(s) . This work is published by BioImpacts as an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([http://creativecommons.org/licenses/by-nc/4.0/](http://creativecommons.org","cbCaikqcjQliIbPi","https://ap.wps.com/l/cbCaikqcjQliIbPi","pdf",1616552,15,"English","# Introduction\n## Tumor microenvironment (TME) and cancer progression\n## Limitations of conventional therapies and TME-driven resistance\n## Self-organization concepts within the TME\n# Methods\n## Literature search strategy and databases\n# Results\n## Disrupting TME self-organization to improve outcomes\n## Biophysical TME properties in therapy development\n# Conclusion\n## Targeting ECM and immune cells to enhance therapy","[{\"question\":\"What role does the tumor microenvironment (TME) play in cancer progression?\",\"answer\":\"The TME drives tumor initiation, growth, invasion, metastasis, angiogenesis, immune evasion, and therapeutic resistance through interactions among extracellular matrix components, cancer cells, non-cancer cells, and soluble factors.\"},{\"question\":\"How does self-organization in the TME contribute to therapy resistance?\",\"answer\":\"Self-organization involves reciprocal interactions between tumor cells and their microenvironment, forming complex structures that support tumor survival and contribute to resistance against anticancer therapies.\"},{\"question\":\"Which therapeutic directions are highlighted by the review?\",\"answer\":\"Targeting extracellular matrix (ECM) components and immune cells within the TME, and focusing on molecules involved in TME self-organization, are proposed to improve treatment effectiveness and help defeat drug resistance.\"}]","The role of tumor microenvironment and self-organization in cancer progression - Key insights for therapeutic development | PDF",1790038909,38]