{"title":"The Tumor Microenvironment: Impact on Tumor Growth, Metastasis, and Therapeutic Resistance: A Systematic Review.","authors":"Jiazhi Yan, Shuo Tu","doi":"10.2174/0115665240388282250903221303","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>This systematic review assesses the role of the tumor microenvironment (TME) in cancer progression and therapy resistance by defining drug-microenvironment interactions and determining the molecular determinants in the TME that could help improve the efficacy of administered treatments and alleviate existing adverse effects.</p><p><strong>Methods: </strong>This systematic review follows the PRISMA protocol and the PICOS selection framework to retrieve studies from PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. Only original human-related research published in English between 2008 and 2023 was used to explore the reciprocal relation between tumor cells and TME components. The ROBINS-I tool assessed the risk of bias.</p><p><strong>Results: </strong>Out of 258 articles initially identified, 15 met the inclusion criteria for this review. The results showed that TMEs significantly influence treatment outcomes in cancer progression, metastasis, and drug resistance. Focusing on TMEs like CAFs, immune cells, and ECM enhances drug efficacy. The study highlighted potential strategies to improve drug delivery, suppress metastatic processes, and restore immune function, ultimately leading to better outcomes for cancer patients.</p><p><strong>Discussion: </strong>Original evidence suggests that Cancer-Associated Fibroblasts (CAFs), immune cells, and Extracellular Matrix (ECM) contribute to therapeutic resistance and metastasis within the TME. They also promote metastasis by inducing Epithelial- Mesenchymal Transition (EMT) and affecting Cancer Stem Cell (CSC) populations. Moreover, the immunosuppressive TME consists of regulatory T cells and myeloidderived suppressor cells that allow tumors to evade the immune system, a concern for immunotherapy.</p><p><strong>Conclusion: </strong>The TME plays a vital role in cancer development, metastasis formation, and therapy failure. The perspectives for innovative ECM-modulating treatments and interventions targeting the direct interactions between TME and cancer cells can be revolutionary and suggest better outcomes for treatment-naïve and refractory cancers. Future research should use these results as inputs to apply clinical and therapy studies to enhance cancer management outcomes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115665240388282250903221303","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: This systematic review assesses the role of the tumor microenvironment (TME) in cancer progression and therapy resistance by defining drug-microenvironment interactions and determining the molecular determinants in the TME that could help improve the efficacy of administered treatments and alleviate existing adverse effects.
Methods: This systematic review follows the PRISMA protocol and the PICOS selection framework to retrieve studies from PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. Only original human-related research published in English between 2008 and 2023 was used to explore the reciprocal relation between tumor cells and TME components. The ROBINS-I tool assessed the risk of bias.
Results: Out of 258 articles initially identified, 15 met the inclusion criteria for this review. The results showed that TMEs significantly influence treatment outcomes in cancer progression, metastasis, and drug resistance. Focusing on TMEs like CAFs, immune cells, and ECM enhances drug efficacy. The study highlighted potential strategies to improve drug delivery, suppress metastatic processes, and restore immune function, ultimately leading to better outcomes for cancer patients.
Discussion: Original evidence suggests that Cancer-Associated Fibroblasts (CAFs), immune cells, and Extracellular Matrix (ECM) contribute to therapeutic resistance and metastasis within the TME. They also promote metastasis by inducing Epithelial- Mesenchymal Transition (EMT) and affecting Cancer Stem Cell (CSC) populations. Moreover, the immunosuppressive TME consists of regulatory T cells and myeloidderived suppressor cells that allow tumors to evade the immune system, a concern for immunotherapy.
Conclusion: The TME plays a vital role in cancer development, metastasis formation, and therapy failure. The perspectives for innovative ECM-modulating treatments and interventions targeting the direct interactions between TME and cancer cells can be revolutionary and suggest better outcomes for treatment-naïve and refractory cancers. Future research should use these results as inputs to apply clinical and therapy studies to enhance cancer management outcomes.
本系统综述通过定义药物-微环境相互作用和确定TME中的分子决定因素来评估肿瘤微环境（TME）在癌症进展和治疗耐药中的作用，TME可以帮助提高所给治疗的疗效并减轻现有的不良反应。方法：本系统综述遵循PRISMA协议和PICOS选择框架，从PubMed/MEDLINE、Web of Science、Scopus和Cochrane图书馆检索研究。仅使用2008年至2023年间发表的英文原始人类相关研究来探索肿瘤细胞与TME成分之间的互反关系。ROBINS-I工具评估偏倚风险。结果：在最初确定的258篇文章中，有15篇符合本综述的纳入标准。结果显示，TMEs显著影响肿瘤进展、转移和耐药的治疗结果。专注于TMEs如CAFs、免疫细胞和ECM可以提高药物疗效。该研究强调了改善药物输送、抑制转移过程和恢复免疫功能的潜在策略，最终为癌症患者带来更好的结果。讨论：原始证据表明，癌症相关成纤维细胞（CAFs）、免疫细胞和细胞外基质（ECM）有助于TME内的治疗耐药和转移。它们还通过诱导上皮-间充质转化（EMT）和影响癌症干细胞（CSC）群体来促进转移。此外，免疫抑制性TME由调节性T细胞和骨髓源性抑制细胞组成，这些细胞允许肿瘤逃避免疫系统，这是免疫治疗的一个关注点。结论：TME在肿瘤的发展、转移形成和治疗失败中起重要作用。针对TME和癌细胞之间直接相互作用的创新ecm调节治疗和干预措施的前景可能是革命性的，并为treatment-naïve和难治性癌症提供更好的结果。未来的研究应将这些结果作为应用临床和治疗研究的输入，以提高癌症管理的结果。
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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