An advanced discrete state–discrete event multiscale simulation model of the response of a solid tumor to chemotherapy: Mimicking a clinical study
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| Název: | An advanced discrete state–discrete event multiscale simulation model of the response of a solid tumor to chemotherapy: Mimicking a clinical study |
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| Autoři: | Stamatakos, G S, Kolokotroni, E A, Dionysiou, D D, Georgiadi, E Ch, Desmedt, Christine |
| Zdroj: | Journal of Theoretical Biology. 266:124-139 |
| Informace o vydavateli: | Elsevier BV, 2010. |
| Rok vydání: | 2010 |
| Témata: | 0301 basic medicine, DNA-Binding Proteins -- genetics, Breast Neoplasms -- drug therapy, Neoplastic Stem Cells -- cytology -- drug effects, Gene Expression, Apoptosis, Breast Neoplasms, Gene Expression -- genetics, Cancer modeling, Models, Biological, Epirubicin -- administration & dosage -- pharmacology -- therapeutic use, Neoplasms -- drug therapy -- metabolism -- pathology, Cell Proliferation -- drug effects, Necrosis, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Models, Antigens, Neoplasm, Software Design, Neoplasms, Chemotherapy, Humans, Computer Simulation, Antigens, Precision Medicine, Cell Proliferation, Epirubicin, Clinical Trials as Topic, Cell Cycle, Biological, Individualized Medicine -- methods, Necrosis -- metabolism -- pathology, 3. Good health, Cancérologie, Apoptosis -- drug effects -- physiology, In silico oncology, DNA-Binding Proteins, Treatment Outcome, DNA Topoisomerases, Type II, Neoplastic Stem Cells, Female, Neoplasm -- genetics, Type II -- genetics, DNA Topoisomerases, Simulation, Algorithms, Cell Cycle -- drug effects -- physiology |
| Popis: | In this paper an advanced, clinically oriented multiscale cancer model of breast tumor response to chemotherapy is presented. The paradigm of early breast cancer treated by epirubicin according to a branch of an actual clinical trial (the Trial of Principle, TOP trial) has been addressed. The model, stemming from previous work of the In Silico Oncology Group, National Technical University of Athens, is characterized by several crucial new features, such as the explicit distinction of proliferating cells into stem cells of infinite mitotic potential and cells of limited proliferative capacity, an advanced generic cytokinetic model and an improved tumor constitution initialization technique. A sensitivity analysis regarding critical parameters of the model has revealed their effect on the behavior of the biological system. The favorable outcome of an initial step towards the clinical adaptation and validation of the simulation model, based on the use of anonymized data from the TOP clinical trial, is presented and discussed. Two real clinical cases from the TOP trial with variable molecular profile have been simulated. A realistic time course of the tumor diameter and a reduction in tumor size in agreement with the clinical data has been achieved for both cases by selection of reasonable model parameter values, thus demonstrating a possible adaptation process of the model to real clinical trial data. Available imaging, histological, molecular and treatment data are exploited by the model in order to strengthen patient individualization modeling. The expected use of the model following thorough clinical adaptation, optimization and validation is to simulate either several candidate treatment schemes for a particular patient and support the selection of the optimal one or to simulate the expected extent of tumor shrinkage for a given time instant and decide on the adequacy or not of the simulated scheme. |
| Druh dokumentu: | Article |
| Popis souboru: | 1 full-text file(s): application/pdf |
| Jazyk: | English |
| ISSN: | 0022-5193 |
| DOI: | 10.1016/j.jtbi.2010.05.019 |
| Přístupová URL adresa: | https://hal.archives-ouvertes.fr/hal-00613132/file/PEER_stage2_10.1016%252Fj.jtbi.2010.05.019.pdf https://pubmed.ncbi.nlm.nih.gov/20515697 https://difusion.ulb.ac.be/vufind/Record/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/118214/Details http://www.sciencedirect.com/science/article/pii/S0022519310002547 https://ui.adsabs.harvard.edu/abs/2010JThBi.266..124S/abstract https://europepmc.org/article/MED/20515697 https://www.ncbi.nlm.nih.gov/pubmed/20515697 https://www.sciencedirect.com/science/article/pii/S0022519310002547 |
| Rights: | Elsevier TDM |
| Přístupové číslo: | edsair.doi.dedup.....adc689401540dfd8c0923ee5aebf74d6 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | In this paper an advanced, clinically oriented multiscale cancer model of breast tumor response to chemotherapy is presented. The paradigm of early breast cancer treated by epirubicin according to a branch of an actual clinical trial (the Trial of Principle, TOP trial) has been addressed. The model, stemming from previous work of the In Silico Oncology Group, National Technical University of Athens, is characterized by several crucial new features, such as the explicit distinction of proliferating cells into stem cells of infinite mitotic potential and cells of limited proliferative capacity, an advanced generic cytokinetic model and an improved tumor constitution initialization technique. A sensitivity analysis regarding critical parameters of the model has revealed their effect on the behavior of the biological system. The favorable outcome of an initial step towards the clinical adaptation and validation of the simulation model, based on the use of anonymized data from the TOP clinical trial, is presented and discussed. Two real clinical cases from the TOP trial with variable molecular profile have been simulated. A realistic time course of the tumor diameter and a reduction in tumor size in agreement with the clinical data has been achieved for both cases by selection of reasonable model parameter values, thus demonstrating a possible adaptation process of the model to real clinical trial data. Available imaging, histological, molecular and treatment data are exploited by the model in order to strengthen patient individualization modeling. The expected use of the model following thorough clinical adaptation, optimization and validation is to simulate either several candidate treatment schemes for a particular patient and support the selection of the optimal one or to simulate the expected extent of tumor shrinkage for a given time instant and decide on the adequacy or not of the simulated scheme. |
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| ISSN: | 00225193 |
| DOI: | 10.1016/j.jtbi.2010.05.019 |