{"title":"具有非线性免疫反应的耐药性演变模型的动态分析。","authors":"Tengfei Wang, Xiufen Zou","doi":"10.1016/j.mbs.2024.109239","DOIUrl":null,"url":null,"abstract":"<div><p>Recent studies have utilized evolutionary mechanisms to impede the emergence of drug-resistant populations. In this paper, we develop a mathematical model that integrates hormonal treatment, immunotherapy, and the interactions among three cell types: drug-sensitive cancer cells, drug-resistant cancer cells and immune effector cells. Dynamical analysis is performed, examining the existence and stability of equilibria, thereby confirming the model’s interpretability. Model parameters are calibrated using available prostate cancer data and literature. Through bifurcation analysis for drug sensitivity under different immune effector cells recruitment responses, we find that resistant cancer cells grow rapidly under weak recruitment response, maintain at a low level under strong recruitment response, and both may occur under moderate recruitment response. To quantify the competitiveness of sensitive and resistant cells, we introduce the comprehensive measures <span><math><msub><mrow><mi>R</mi></mrow><mrow><mn>1</mn></mrow></msub></math></span> and <span><math><msub><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span>, respectively, which determine the outcome of competition. Additionally, we introduce the quantitative indicators <span><math><mrow><mi>C</mi><mi>I</mi><msub><mrow><mi>E</mi></mrow><mrow><mn>1</mn></mrow></msub></mrow></math></span> and <span><math><mrow><mi>C</mi><mi>I</mi><msub><mrow><mi>E</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></math></span> as comprehensive measures of the immune effects on sensitive and resistant cancer cells, respectively. These two indicators determine whether the corresponding cancer cells can maintain at a low level. Our work shows that the immune system is an important factor affecting the evolution of drug resistance and provides insights into how to enhance immune response to control resistance.</p></div>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dynamic analysis of a drug resistance evolution model with nonlinear immune response\",\"authors\":\"Tengfei Wang, Xiufen Zou\",\"doi\":\"10.1016/j.mbs.2024.109239\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Recent studies have utilized evolutionary mechanisms to impede the emergence of drug-resistant populations. In this paper, we develop a mathematical model that integrates hormonal treatment, immunotherapy, and the interactions among three cell types: drug-sensitive cancer cells, drug-resistant cancer cells and immune effector cells. Dynamical analysis is performed, examining the existence and stability of equilibria, thereby confirming the model’s interpretability. Model parameters are calibrated using available prostate cancer data and literature. Through bifurcation analysis for drug sensitivity under different immune effector cells recruitment responses, we find that resistant cancer cells grow rapidly under weak recruitment response, maintain at a low level under strong recruitment response, and both may occur under moderate recruitment response. To quantify the competitiveness of sensitive and resistant cells, we introduce the comprehensive measures <span><math><msub><mrow><mi>R</mi></mrow><mrow><mn>1</mn></mrow></msub></math></span> and <span><math><msub><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msub></math></span>, respectively, which determine the outcome of competition. Additionally, we introduce the quantitative indicators <span><math><mrow><mi>C</mi><mi>I</mi><msub><mrow><mi>E</mi></mrow><mrow><mn>1</mn></mrow></msub></mrow></math></span> and <span><math><mrow><mi>C</mi><mi>I</mi><msub><mrow><mi>E</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></math></span> as comprehensive measures of the immune effects on sensitive and resistant cancer cells, respectively. These two indicators determine whether the corresponding cancer cells can maintain at a low level. Our work shows that the immune system is an important factor affecting the evolution of drug resistance and provides insights into how to enhance immune response to control resistance.</p></div>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0025556424000993\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0025556424000993","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Dynamic analysis of a drug resistance evolution model with nonlinear immune response
Recent studies have utilized evolutionary mechanisms to impede the emergence of drug-resistant populations. In this paper, we develop a mathematical model that integrates hormonal treatment, immunotherapy, and the interactions among three cell types: drug-sensitive cancer cells, drug-resistant cancer cells and immune effector cells. Dynamical analysis is performed, examining the existence and stability of equilibria, thereby confirming the model’s interpretability. Model parameters are calibrated using available prostate cancer data and literature. Through bifurcation analysis for drug sensitivity under different immune effector cells recruitment responses, we find that resistant cancer cells grow rapidly under weak recruitment response, maintain at a low level under strong recruitment response, and both may occur under moderate recruitment response. To quantify the competitiveness of sensitive and resistant cells, we introduce the comprehensive measures and , respectively, which determine the outcome of competition. Additionally, we introduce the quantitative indicators and as comprehensive measures of the immune effects on sensitive and resistant cancer cells, respectively. These two indicators determine whether the corresponding cancer cells can maintain at a low level. Our work shows that the immune system is an important factor affecting the evolution of drug resistance and provides insights into how to enhance immune response to control resistance.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.