New Challenges for Cancer Systems Biomedicine (SEMA SIMAI Springer Series Book 1)

The future of oncology seems to lie in Molecular Medicine (MM). MM is a new science based on three pillars. Two of them are evident in its very name and are well known: medical science and molecular biology. However, there is a general unawareness that MM is firmly based on a third, and equally important, pillar: Systems Biomedicine. Currently, this term denotes multilevel, hierarchical models integrating key factors at the molecular, cellular, tissue, through phenotype levels, analyzed to reveal the global behavior of the biological process under consideration. It becomes increasingly evident that the tools to construct such complex models include, not only bioinformatics and modern applied statistics, as is unanimously agreed, but also other interdisciplinary fields of science, notably, Mathematical Oncology, Systems Biology and Theoretical Biophysics. Front Matter....Pages i-xi Front Matter....Pages 1-1 Combining Game Theory and Graph Theory to Model Interactions between Cells in the Tumor Microenvironment....Pages 3-18 Growth as the Root of all Evil in Carcinomas: Synergy between pH Buffering and Anti-Angiogenesis Prevents Emergence of Hallmarks of Cancer....Pages 19-34 Phase Transitions in Cancer....Pages 35-51 Front Matter....Pages 53-53 Spatio-Temporal Modelling of Intracellular Signalling Pathways: Transcription Factors, Negative Feedback Systems and Oscillations....Pages 55-82 Understanding Cell Fate Decisions by Identifying Crucial System Dynamics....Pages 83-104 Modelling Biochemical Pathways with the Calculus of Looping Sequences....Pages 105-125 Dynamic Simulations of Pathways Downstream of TGF β , Wnt and EGF-Family Growth Factors, in Colorectal Cancer, including Mutations and Treatments with Onco-Protein Inhibitors....Pages 127-142 Front Matter....Pages 143-143 Some Results on the Population Behavior of Cancer Stem Cells....Pages 145-172 Glucose Metabolism in Multicellular Spheroids, ATP Production and Effects of Acidity....Pages 173-190 Cell-Cell Interactions in Solid Tumors — the Role of Cancer Stem Cells....Pages 191-204 Hybrid Cellular Potts Model for Solid Tumor Growth....Pages 205-224 Front Matter....Pages 225-225 Computational Models as Novel Tools for Cancer Vaccines....Pages 227-248 On the Dynamics of Tumor-Immune System Interactions and Combined Chemo- and Immunotherapy....Pages 249-266 Modeling the Kinetics of the Immune Response....Pages 267-282 Front Matter....Pages 283-283 Optimizing Cancer Chemotherapy: From Mathematical Theories to Clinical Treatment....Pages 285-299 A Systems Biomedicine Approach for Chronotherapeutics Optimization: Focus on the Anticancer Drug Irinotecan....Pages 301-327 Modeling the Dynamics of HCV Infected Cells to Tailor Antiviral Therapy in Clinical Practice: Can This Approach Fit for Neoplastic Cells?....Pages 329-336 Introducing Drug Transport Early in the Design of Hypoxia Selective Anticancer Agents Using a Mathematical Modelling Approach....Pages 337-353 Top-Down Multiscale Simulation of Tumor Response to Treatment in the Context of In Silico Oncology. The Notion of Oncosimulator ....Pages 355-375 Challenges in the Integration of Flow Cytometry and Time-Lapse Live Cell Imaging Data Using a Cell Proliferation Model....Pages 376-398 Part I Towards a Comprehensive Theory of Cancer Growth Combining Game Theory and Graph Theory to Model Interactions between Cells in the Tumor Microenvironment Growth as the Root of all Evil in Carcinomas: Synergy between pH Buffering and Anti-Angiogenesis prevents Emergence of Hallmarks of Cancer Phase Transitions in Cancer Part II Cancer Related Signalling Pathways Spatio-Temporal Modelling of Intracellular Signalling Pathways: Transcription Factors, Negative Feedback Systems and Oscillations Understanding Cell Fate Decisions by Identifying Crucial System Dynamics Modelling Biochemical Pathways with the Calculus of Looping Sequences Dynamic Simulations of Pathways Downstream of TGFβ, Wnt and EGF-Family Growth Factors, in Colorectal Cancer, including Mutations and Treatments with Onco-Protein Inhibitors Part III Basic Mechanisms of Tumor Progression Some Results on the Population Behavior of Cancer Stem Cells ^ Glucose Metabolism in Multicellular Spheroids, ATP Production and Effects of Acidity Cell-Cell Interactions in Solid Tumors - the Role of Cancer Stem Cells Hybrid Cellular Potts Model for Solid Tumor Growth Part IV Tumor-Immune System Interplay and Immunotherapy Computational Models as Novel Tools for Cancer Vaccines On the Dynamics of Tumor-Immune System Interactions and Combined Chemo- and Immunotherapy Modeling the Kinetics of the Immune Response Part V Computational Method for Improving Chemotherapy.- Optimizing Cancer Chemotherapy: from Mathematical Theories to Clinical Treatment A Systems Biomedicine Approach for Chronotherapeutics Optimization: Focus on the Anticancer Drug Irinotecan Modeling the Dynamics of HCV Infected Cells to Tailor Antiviral Therapy in Clinical Practice: Can This Approach Fit for Neoplastic Cells? Introducing Drug Transport Early in the Design of Hypoxia Selective Anticancer Agents Using a Mathematical Modelling Approach ^ ^^ Top-Down Multiscale Simulation of Tumor Response to Treatment in the Context of In Silico Oncology. The Notion of Oncosimulator Challenges in the Integration of Flow Cytometry and Time-Lapse Live Cell Imaging Data Using a Cell Proliferation Model. ^^ The aim of this book is not only to illustrate the state of the art of tumor systems biomedicine, but also and mainly to explicitly capture the fact that a increasing number of biomedical scientists is now directly working on mathematical modeling, and a larger number are collaborating with bio-mathematical scientists. Moreover, a number of biomathematicians started working in biomedical institutions. The book is characterized by a coherent view of tumor modeling, based on the concept that mathematical modeling is (with medicine and molecular biology) one of the three pillars of molecular medicine. Indeed this volume is characterized by a well-structured presence of a large number of biomedical scientists directly working in Mathematical or Systems Biomedicine, and of a number biomathematicians working in hospitals. This give to this book an unprecedented tone, providing an original interdisciplinary insight into the biomedical applications. Finally, all biomedical contributors were asked to briefly summarize in one section of their contributes their point of view on her/his own interactions with quantitative scientists working in Systems Biomedicine.