{"title":"Malignant melanoma fractional-order mathematical model with stabilized fuzzy sliding mode control","authors":"David Amilo, Khadijeh Sadri, Evren Hincal","doi":"10.1016/j.cmpb.2025.108912","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and Objective:</h3><div>Malignant melanoma, an aggressive form of skin cancer, poses significant challenges due to its rapid progression, metastatic potential, and resistance to therapies. This study aims to develop a fractional-order mathematical model capturing melanoma dynamics (tumor-immune interactions, extracellular matrix remodeling, nutrient dynamics) and introduce a Stabilized Fuzzy Sliding Mode Control (SFSMC) strategy to suppress tumor growth and restore microenvironmental homeostasis.</div></div><div><h3>Methods:</h3><div>A fractional-order model was derived using Caputo derivatives to incorporate memory effects and long-range dependencies. The SFSMC combines sliding mode control with fuzzy logic to manage uncertainties. Theoretical analysis included well-posedness, stability (via Lyapunov functions), and computation of the reproduction number <span><math><msub><mrow><mi>R</mi></mrow><mrow><mn>0</mn></mrow></msub></math></span>. Numerical simulations were performed using a predictor–corrector method with parameters calibrated from clinical data.</div></div><div><h3>Results:</h3><div>The model demonstrated stability when <span><math><mrow><msub><mrow><mi>R</mi></mrow><mrow><mn>0</mn></mrow></msub><mo><</mo><mn>1</mn></mrow></math></span>, indicating tumor suppression. SFSMC reduced tumor cell populations by 78% and circulating tumor cells by 65% while improving immune response (45% increase in immune cells) and nutrient availability (30% recovery). Sensitivity analysis revealed <span><math><msub><mrow><mi>R</mi></mrow><mrow><mn>0</mn></mrow></msub></math></span> is mostly influenced by tumor growth rate, natural degradation rate of extracellular matrix (ECM), rate of ECM degradation by tumor cells, and ECM production rate, suggesting their potential role in suppressing tumor growth.</div></div><div><h3>Conclusions:</h3><div>The fractional-order framework and SFSMC offer a robust approach to modeling and controlling melanoma, with potential clinical implications for adaptive therapy.</div></div>","PeriodicalId":10624,"journal":{"name":"Computer methods and programs in biomedicine","volume":"270 ","pages":"Article 108912"},"PeriodicalIF":4.9000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computer methods and programs in biomedicine","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0169260725003293","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS","Score":null,"Total":0}
引用次数: 0
Abstract
Background and Objective:
Malignant melanoma, an aggressive form of skin cancer, poses significant challenges due to its rapid progression, metastatic potential, and resistance to therapies. This study aims to develop a fractional-order mathematical model capturing melanoma dynamics (tumor-immune interactions, extracellular matrix remodeling, nutrient dynamics) and introduce a Stabilized Fuzzy Sliding Mode Control (SFSMC) strategy to suppress tumor growth and restore microenvironmental homeostasis.
Methods:
A fractional-order model was derived using Caputo derivatives to incorporate memory effects and long-range dependencies. The SFSMC combines sliding mode control with fuzzy logic to manage uncertainties. Theoretical analysis included well-posedness, stability (via Lyapunov functions), and computation of the reproduction number . Numerical simulations were performed using a predictor–corrector method with parameters calibrated from clinical data.
Results:
The model demonstrated stability when , indicating tumor suppression. SFSMC reduced tumor cell populations by 78% and circulating tumor cells by 65% while improving immune response (45% increase in immune cells) and nutrient availability (30% recovery). Sensitivity analysis revealed is mostly influenced by tumor growth rate, natural degradation rate of extracellular matrix (ECM), rate of ECM degradation by tumor cells, and ECM production rate, suggesting their potential role in suppressing tumor growth.
Conclusions:
The fractional-order framework and SFSMC offer a robust approach to modeling and controlling melanoma, with potential clinical implications for adaptive therapy.
期刊介绍:
To encourage the development of formal computing methods, and their application in biomedical research and medical practice, by illustration of fundamental principles in biomedical informatics research; to stimulate basic research into application software design; to report the state of research of biomedical information processing projects; to report new computer methodologies applied in biomedical areas; the eventual distribution of demonstrable software to avoid duplication of effort; to provide a forum for discussion and improvement of existing software; to optimize contact between national organizations and regional user groups by promoting an international exchange of information on formal methods, standards and software in biomedicine.
Computer Methods and Programs in Biomedicine covers computing methodology and software systems derived from computing science for implementation in all aspects of biomedical research and medical practice. It is designed to serve: biochemists; biologists; geneticists; immunologists; neuroscientists; pharmacologists; toxicologists; clinicians; epidemiologists; psychiatrists; psychologists; cardiologists; chemists; (radio)physicists; computer scientists; programmers and systems analysts; biomedical, clinical, electrical and other engineers; teachers of medical informatics and users of educational software.