| تعداد نشریات | 34 |
| تعداد شمارهها | 460 |
| تعداد مقالات | 4,376 |
| تعداد مشاهده مقاله | 6,811,119 |
| تعداد دریافت فایل اصل مقاله | 6,659,277 |
Integrated Computational Frameworks for Multiscale Modeling of Cancer Prevention: A Review | ||
| Biological Data | ||
| دوره 1، شماره 1، شهریور 2026، صفحه 20-43 اصل مقاله (741.08 K) | ||
| نوع مقاله: Review Article | ||
| نویسندگان | ||
| Elahe Ghiyabi* 1؛ Houshang Shaker Nigjeh2؛ Sajjad Mortazavi1 | ||
| 1Department of Biomedical Engineering, Faculty of Electrical and Computer Engineering, University of Tabriz, Tabriz, Iran | ||
| 2Department of Biomedical Engineering, Faculty of Electrical and Computer Engineering, University of Zanjan, Zanjan, Iran | ||
| چکیده | ||
| Cancer develops through interconnected molecular, cellular, and tissue-level processes that span multiple spatial and temporal scales. Although multiscale experimental data have expanded opportunities for quantitative analysis, challenges such as limited data availability, biological heterogeneity, and the need for interpretable predictions still restrict progress. A broad range of mathematical and computational approaches has been developed to address these issues. Population-level models based on ordinary differential equations remain central to studies of tumor growth, immune dynamics, and treatment effects, while stochastic versions capture uncertainty in early carcinogenic events and variability in therapeutic outcomes. Spatially resolved methods, including partial differential equations, cellular automata, and multiphase models, incorporate microenvironmental heterogeneity, chemical gradients, and mechanical influences that shape tumor behavior. At the cellular scale, agent-based models represent heterogeneous populations and local interactions, and intracellular network models together with evolutionary game-theoretic approaches clarify regulatory mechanisms and competitive dynamics. Recent efforts increasingly focus on hybrid and multiscale frameworks that integrate these strategies to connect molecular events with emergent tissue-level patterns. This review examines how cancer develops across interconnected molecular, cellular, and tissue-level processes spanning multiple spatial and temporal scales. | ||
| کلیدواژهها | ||
| Cancer Prevention؛ Agent-Based Model (ABM)؛ Multi-scale Modeling؛ Computational Oncology؛ Digital Twins | ||
| مراجع | ||
|
Acharya, D., & Mukhopadhyay, A. (2024). A comprehensive review of machine learning techniques for multi-omics data integration: Challenges and applications in precision oncology. Briefings in Functional Genomics, 23(5), 549-560. https://doi.org/10.1093/bfgp/elae013
Agnello, A., Amorisco, N.C., Keats, A., Holt, G.K., Buchanan, J., Pamela, S., Vincent, C., & McArdle, G. (2024). Emulation techniques for scenario and classical control design of tokamak plasmas. Physics of Plasmas, 31(4), 1-12. https://doi.org/10.1063/5.0187822
Ali, H. (2023). Artificial intelligence in multi-omics data integration: Advancing precision medicine, biomarker discovery and genomic-driven disease interventions. International Journal of Science and Research Archive, 8(1), 1012-1030. https://doi.org/10.30574/ijsra.2023.8.1.0189
Alkim, E., Dowst, H., DiCarlo, J., Dobrolecki, L.E., Hernández-Herrera, A., Hormuth, D.A., Liao, Y., McOwiti, A., Pautler, R., & Rimawi, M. (2023). Toward practical integration of omic and imaging data in co-clinical trials. Tomography, 9(2), 810-828. https://doi.org/10.3390/tomography9020066
Altrock, P.M., Liu, L.L., & Michor, F. (2015). The mathematics of cancer: Integrating quantitative models. Nature Reviews Cancer, 15(12), 730-745. https://doi.org/10.1038/nrc4029
Anderson, A.R., & Quaranta, V. (2008). Integrative mathematical oncology. Nature Reviews Cancer, 8(3), 227-234. https://doi.org/10.1038/nrc2329
Azizi, T. (2024). Mathematical modeling of cancer progression. AppliedMath, 4(3), 1065-1079. https://doi.org/10.3390/appliedmath4030057
Azizi, T. (2025). Mathematical modelling of cancer treatments, resistance, optimization. AppliedMath, 5(2), 40. https://doi.org/10.3390/appliedmath5020040
Baião, A., Cai, Z., Poulos, R., Robinson, P., Reddel, R., Zhong, Q., Vinga, S., & Gonçalves, E. (2025). A technical review of multi-omics data integration methods: From classical statistical to deep generative approaches. Briefings in Bioinformatics, 26(4), bbaf355. https://doi.org/10.1093/bib/bbaf355
Barabasi, A.L., & Oltvai, Z.N. (2004). Network biology: understanding the cell's functional organization. Nature Reviews Genetics, 5(2), 101-113. https://doi.org/10.1038/nrg1272
Bora, Ş., & Emek, S. (2019). Agent-based modeling and simulation of biological systems. Computer Simulation, IntechOpen. 1-17. https://doi.org/10.5772/intechopen.80070
Brunton, S.L., & Kutz, J.N. (2022). Data-driven science and engineering: Machine learning, dynamical systems, and control. Cambridge University Press. https://doi.org/10.1017/9781108380690
Butner, J.D., Dogra, P., Chung, C., Koay, E.J., Welsh, J.W., Hong, D.S., Cristini, V., & Wang, Z. (2024). Hybridizing mechanistic modeling and deep learning for personalized survival prediction after immune checkpoint inhibitor immunotherapy. npj Systems Biology and Applications, 10, 88. https://doi.org/10.1038/s41540-024-00415-8
Byrne, H.M. (2010). Dissecting cancer through mathematics: from the cell to the animal model. Nature Reviews Cancer, 10(3), 221-230. https://doi.org/10.1038/nrc2808
Camacho, D.M., Collins, K.M., Powers, R.K., Costello, J.C., & Collins, J.J. (2018). Next-generation machine learning for biological networks. Cell, 173(7), 1581-1592. https://doi.org/10.1016/j.cell.2018.05.015
Chamseddine, I.M., & Rejniak, K.A. (2020). Hybrid modeling frameworks of tumor development and treatment. Wiley Interdisciplinary Reviews Systems Biology and Medicine, 12(1), e1461. https://doi.org/10.1002/wsbm.1461
Chaudhuri, A., Pash, G., Hormuth, D.A., Lorenzo, G., Kapteyn, M., Wu, C., Lima, E.A.B.F., Yankeelov, T.E., & Willcox, K. (2023). Predictive digital twin for optimizing patient-specific radiotherapy regimens under uncertainty in high-grade gliomas. Frontiers in Artificial Intelligence, 6, 1222612. https://doi.org/10.3389/frai.2023.1222612
Clarke, R., Tyson, J.J., Tan, M., Baumann, W.T., Jin, L., Xuan, J., & Wang, Y. (2019). Systems biology: Perspectives on multiscale modeling in research on endocrine-related cancers. Endocrine-Related Cancer, 26(6), R345-R368. https://doi.org/10.1530/ERC-18-0309
Croatti, A., Gabellini, M., Montagna, S., & Ricci, A. (2020). On the integration of agents and digital twins in healthcare. Journal of Medical Systems, 44(9), 161. https://doi.org/10.1007/s10916-020-01623-5
Deisboeck, T.S., Wang, Z., Macklin, P., & Cristini, V. (2011). Multiscale cancer modeling. Annual Review of Biomedical Engineering, 13, 127-155. https://doi.org/10.1146/annurev-bioeng-071910-124729
Farhadizadeh, M., Weymann, M., Blaß, M., Kraus, J., Gundler, C., Walter, S., Hempen, N., Binder, H., & Binder, N. (2025). A systematic review of challenges and proposed solutions in modeling multimodal data. arXiv, 1-49. https://doi.org/10.48550/arXiv.2505.06945
Fumia, H.F., & Martins, M.L. (2013). Boolean network model for cancer pathways: Predicting carcinogenesis and targeted therapy outcomes. PloS One, 8(7), e69008. https://doi.org/10.1371/journal.pone.0069008
Gatenby, R.A., & Vincent, T.L. (2003a). Application of quantitative models from population biology and evolutionary game theory to tumor therapeutic strategies. Molecular Cancer Therapeutics, 2(9), 919-927.
Gatenby, R.A., & Vincent, T.L. (2003b). An evolutionary model of carcinogenesis. Cancer Research, 63(19), 6212-6220.
Gerlee, P., & Anderson, A.R. (2007). An evolutionary hybrid cellular automaton model of solid tumour growth. Journal of Theoretical Biology, 246(4), 583-603. https://doi.org/10.1016/j.jtbi.2007.01.027
Ghassemi, M., Naumann, T., Schulam, P., Beam, A.L., Chen, I.Y., & Ranganath, R. (2020). A review of challenges and opportunities in machine learning for health. AMIA Summits on Translational Science Proceedings, 2020, 191-200.
Gherman, I.M., Abdallah, Z.S., Pang, W., Gorochowski, T.E., Grierson, C.S., & Marucci, L. (2023). Bridging the gap between mechanistic biological models and machine learning surrogates. PLos Computational Biology, 19(4), e1010988. https://doi.org/10.1371/journal.pcbi.1010988
Gonçalves, I.G., & García-Aznar, J.M. (2023). Hybrid computational models of multicellular tumour growth considering glucose metabolism. Computational and Structural Biotechnology Journal, 21, 1262-1271. https://doi.org/10.1016/j.csbj.2023.01.044
Gong, C., Milberg, O., Wang, B., Vicini, P., Narwal, R., Roskos, L., & Popel, A.S. (2017). A computational multiscale agent-based model for simulating spatio-temporal tumour immune response to PD1 and PDL1 inhibition. Journal of the Royal Society Interface, 14(134), 20170320. https://doi.org/10.1098/rsif.2017.0320
Grimm, V., Revilla, E., Berger, U., Jeltsch, F., Mooij, W.M., Railsback, S.F., Thulke, H.H., Weiner, J., Wiegand, T., & DeAngelis, D.L. (2005). Pattern-oriented modeling of agent-based complex systems: Lessons from ecology. Science, 310(5750), 987-991. https://doi.org/10.1126/science.1116681
Gross, F., & MacLeod, M. (2017). Prospects and problems for standardizing model validation in systems biology. Progress in Niophysics and Molecular Biology, 129, 3-12. https://doi.org/10.1016/j.pbiomolbio.2017.01.003
Hallek, M. (2025). Chronic Lymphocytic Leukemia: 2025 update on the epidemiology, pathogenesis, diagnosis, and therapy. American Journal of Hematology, 100(3), 450–480. https://doi.org/10.1002/ajh.27546
Hanahan, D. (2022). Hallmarks of cancer: New dimensions. Cancer Discovery, 12(1), 31-46. https://doi.org/10.1158/2159-8290.CD-21-1059
Hickey, J.W., Agmon, E., Horowitz, N., Lamore, M., Sunwoo, J., Covert, M., & Nolan, G.P. (2023). Integrating multiplexed imaging and multiscale modeling identifies tumor phenotype transformation as a critical component of therapeutic T cell efficacy. BioRxiv, 12.06.570168. https://doi.org/10.1101/2023.12.06.570168
Hsu, C.Y., Askar, S., Alshkarchy, S.S., Nayak, P.P., Attabi, K.A., Khan, M.A., Mayan, J.A., Sharma, M., Islomov, S., & Soleimani Samarkhazan, H. (2026). AI-driven multi-omics integration in precision oncology: bridging the data deluge to clinical decisions. Clinical and Experimental Medicine, 26, 29. https://doi.org/10.1007/s10238-025-01965-9
Huang, S., Ernberg, I., & Kauffman, S. (2009). Cancer attractors: A systems view of tumors from a gene network dynamics and developmental perspective. Seminars in Cell & Developmental Biology, 20(7), 869-876. https://doi.org/10.1016/j.semcdb.2009.07.003
Jarrett, A.M., Lima, E.A.B.F., Hormuth, D.A., McKenna, M.T., Feng, X., Ekrut, D.A., Resende, A.C.M., Brock, A., & Yankeelov, T.E. (2018). Mathematical models of tumor cell proliferation: A review of the literature. Expert Review of Anticancer Therapy, 18(12), 1271-1286. https://doi.org/10.1080/14737140.2018.1527689
Kansal, A.R., Torquato, S., Harsh, G.R., Chiocca, E.A., & Deisboeck, T.S. (2000). Simulated brain tumor growth dynamics using a three-dimensional cellular automaton. Journal of Theoretical Biology, 203(4), 367-382. https://doi.org/10.1006/jtbi.2000
Katsaounis, D., Harbour, N., Williams, T., Chaplain, M.A., & Sfakianakis, N. (2024). A genuinely hybrid, multiscale 3d cancer invasion and metastasis modelling framework. Bulletin of Mathematical Biology, 86(6), 64. https://doi.org/10.1007/s11538-024-01286-0
Kaul, R., Ossai, C., Forkan, A.R.M., Jayaraman, P.P., Zelcer, J., Vaughan, S., & Wickramasinghe, N. (2023). The role of AI for developing digital twins in healthcare: The case of cancer care. WIREs Data Mining and Knowledge Discovery, 13(1), e1480. https://doi.org/10.1002/widm.1480
Kreeger, P.K., & Lauffenburger, D.A. (2010). Cancer systems biology: a network modeling perspective. Carcinogenesis, 31(1), 2-8. https://doi.org/10.1093/carcin/bgp261
Li, C., & Lei, J. (2025). Mathematical modeling of tumor-immune interactions: Methods, applications, and future perspectives. arXiv, 1-72. https://doi.org/10.4208/csiam-ls.SO-2024-0008
Metzcar, J., Jutzeler, C.R., Macklin, P., Köhn-Luque, A., & Brüningk, S.C. (2024). A review of mechanistic learning in mathematical oncology. Frontiers in Immunology, 15, 1363144. https://doi.org/10.3389/fimmu.2024.1363144
Metzcar, J., Wang, Y., Heiland, R., & Macklin, P. (2019). A review of cell-based computational modeling in cancer biology. JCO Clinical Cancer Informatics, 3, 1-13. https://doi.org/10.1200/CCI.18.00069
Mirzaei, N.M., & Shahriyari, L. (2024). Modeling cancer progression: An integrated workflow extending data-driven kinetic models to bio-mechanical PDE models. Physical Biology, 21(2), 022001. https://doi.org/10.1088/1478-3975/ad2777
Nardini, J.T., Baker, R.E., Simpson, M.J., & Flores, K.B. (2021). Learning differential equation models from stochastic agent-based model simulations. Journal of the Royal Society Interface, 18(176), 20200987. https://doi.org/10.1098/rsif.2020.0987
Norton, K.A., Gong, C., Jamalian, S., & Popel, A.S. (2019). Multiscale agent-based and hybrid modeling of the tumor immune microenvironment. Processes, 7(1), 37. https://doi.org/10.3390/pr7010037
Poleszczuk, J., Macklin, P., & Enderling, H. (2016). Agent-based modeling of cancer stem cell driven solid tumor growth. In Methods in Molecular Biology, 1516, 335-346. https://doi.org/10.1007/7651-2016-346
Rackauckas, C., Ma, Y., Martensen, J., Warner, C., Zubov, K., Supekar, R., Skinner, D., Ramadhan, A., & Edelman, A. (2020). Universal differential equations for scientific machine learning. arXiv, 1-55. https://doi.org/10.48550/arXiv.2001.04385
Ramis-Conde, I., Chaplain, M.A., & Anderson, A.R. (2008). Mathematical modelling of cancer cell invasion of tissue. Mathematical and Computer Modelling, 47(5-6), 533-545. https://doi.org/10.1016/j.mcm.2007.02.034
Ran, D., Li, J., Zhao, M., Du, L., Zhang, Y., & Zhu, J. (2025). Artificial intelligence integrates multi-omics data for precision stratification and drug resistance prediction in breast cancer. Frontiers in Oncology, 15, 1612474. https://doi.org/10.3389/fonc.2025.1612474
Rejniak, K.A., & Anderson, A.R. (2011). Hybrid models of tumor growth. Wiley Interdiscip Rev Syst Biol Med, 3(1), 115-125. https://doi.org/10.1002/wsbm.102
Rejniak, K.A., & Anderson, A.R. (2011). Hybrid models of tumor growth. WIREs Systems Biology and Medicine, 3(1), 115–125. https://doi.org/10.1002/wsbm.102
Rikard, S.M., Athey, T.L., Nelson, A.R., Christiansen, S.L., Lee, J.J., Holmes, J.W., Peirce, S.M., & Saucerman, J.J. (2019). Multiscale coupling of an agent-based model of tissue fibrosis and a logic-based model of intracellular signaling. Frontiers in Physiology, 10, 1481. https://doi.org/10.3389/fphys.2019.01481
Robertson-Tessi, M., El-Kareh, A., & Goriely, A. (2012). A mathematical model of tumor-immune interactions. Journal of Theoretical Biology, 294, 56-73. https://doi.org/10.1016/j.jtbi.2011.10.027
Rubanova, Y., Chen, R.T.Q., & Duvenaud, D. (2019). Latent ordinary differential equations for irregularly-sampled time series. arXiv, 1-21. https://doi.org/10.48550/arXiv.1907.03907
Ruiz-Martinez, A., Gong, C., Wang, H., Sove, R.J., Mi, H., Kimko, H., & Popel, A.S. (2022). Simulations of tumor growth and response to immunotherapy by coupling a spatial agent-based model with a whole-patient quantitative systems pharmacology model. PLos Computational Biology, 18(7), e1010254. https://doi.org/10.1371/journal.pcbi.1010254
Sancho-Araiz, A., Mangas-Sanjuan, V., & Trocóniz, I.F. (2021). The role of mathematical models in immuno-oncology: challenges and future perspectives. Pharmaceutics, 13(7), 1016. https://doi.org/10.3390/pharmaceutics13071016
Seoni, S., Jahmunah, V., Salvi, M., Barua, P.D., Molinari, F., & Acharya, U.R. (2023). Application of uncertainty quantification to artificial intelligence in healthcare: A review of last decade (2013-2023). Computers in Biology and Medicine, 165, 107441. https://doi.org/10.1016/j.compbiomed.2023.107441
Si, H., Kumar, S., Lata, S., Ahmad, A., Ghosh, S., Stephansen, K., Nagarkar, D., Zhou, E., & Higgs, B.W. (2025). Mechanistically explainable AI model for predicting synergistic cancer therapy combinations. Current Oncology, 32(10), 548. https://doi.org/10.3390/curroncol32100548
Stéphanou, A., Fanchon, E., Innominato, P.F., & Ballesta, A. (2018). Systems biology, systems medicine, systems pharmacology: The what and the why. Acta Biotheoretica, 66, 345-365. https://doi.org/10.1007/s10441-018-9330-2
Sun, X., & Hu, B. (2018). Mathematical modeling and computational prediction of cancer drug resistance. Briefings in Bioinformatics, 19(6), 1382-1399. https://doi.org/10.1093/bib/bbx065
Świerniak, A., & Krześlak, M. (2016). Cancer heterogeneity and multilayer spatial evolutionary games. Biol Direct, 11(1), 53. https://doi.org/10.1186/s13062-016-0156-z
Tomlinson, I., & Bodmer, W. (1997). Modelling the consequences of interactions between tumour cells. British Journal of Cancer, 75(2), 157-160. https://doi.org/10.1038/bjc.1997.26
Villa, C., Maini, P.K., Browning, A.P., Jenner, A.L., Hamis, S., & Cassidy, T. (2025). Reducing phenotype-structured partial differential equations models of cancer evolution to systems of ordinary differential equations: A generalised moment dynamics approach. Journal of Mathematical Biology, 91(2), 22. https://doi.org/10.1007/s00285-025-02246-5
Wang, L.S., Yu, J., Li, S., & Liu, Z. (2025). Analysis and mean-field limit of a hybrid PDE-ABM modeling angiogenesis-regulated resistance evolution. Mathematics, 13(17), 2898. https://doi.org/10.3390/math13172898
Wolfram, S., & Gad-el-Hak, M. (2003). A new kind of science. Applied Mechanics Reviews, 56(2), B18-B19. https://doi.org/10.1115/1.1553433
Wysocka, M., Wysocki, O., Zufferey, M., Landers, D., & Freitas, A. (2023). A systematic review of biologically-informed deep learning models for cancer: Fundamental trends for encoding and interpreting oncology data. BMC Bioinformatics, 24, 198. https://doi.org/10.1186/s12859-023-05262-8
Yankeelov, T.E., An, G., Saut, O., Luebeck, E.G., Popel, A.S., Ribba, B., Vicini, P., Zhou, X., Weis, J.A., & Ye, K. (2016). Multi-scale modeling in clinical oncology: Opportunities and barriers to success. Annals of Biomedical Engineering, 44(9), 2626-2641. https://doi.org/10.1007/s10439-016-1691-6
Zahir, N., Sun, R., Gallahan, D., Gatenby, R.A., & Curtis, C. (2020). Characterizing the ecological and evolutionary dynamics of cancer. Nature Genetics, 52(8), 759-767. https://doi.org/10.1038/s41588-020-0668-4
Zangooei, M.H., & Habibi, J. (2017). Hybrid multiscale modeling and prediction of cancer cell behavior. PloS One, 12(8), e0183810. https://doi.org/10.1371/journal.pone.0183810
Zou, J., Huss, M., Abid, A., Mohammadi, P., Torkamani, A., & Telenti, A. (2019). A primer on deep learning in genomics. Nature genetics, 51(1), 12-18. https://doi.org/10.1038/s41588-018-0295-5 | ||
|
آمار تعداد مشاهده مقاله: 2 |
||