Mathematical Oncology 2013

With chapters on free boundaries, constitutive equations, stochastic dynamics, nonlinear diffusion–consumption, structured populations, and applications of optimal control theory, this volume presents the most significant recent results in the field of mathematical oncology. It highlights the work of world-class research teams, and explores how different researchers approach the same problem in various ways. Tumors are complex entities that present numerous challenges to the mathematical modeler. First and foremost, they grow. Thus their spatial mean field description involves a free boundary problem. Second, their interiors should be modeled as nontrivial porous media using constitutive equations. Third, at the end of anti-cancer therapy, a small number of malignant cells remain, making the post-treatment dynamics inherently stochastic. Fourth, the growth parameters of macroscopic tumors are non-constant, as are the parameters of anti-tumor therapies. Changes in these parameters may induce phenomena that are mathematically equivalent to phase transitions. Fifth, tumor vascular growth is random and self-similar. Finally, the drugs used in chemotherapy diffuse and are taken up by the cells in nonlinear ways. Mathematical Oncology 2013 will appeal to graduate students and researchers in biomathematics, computational and theoretical biology, biophysics, and bioengineering.

Introduction to Mathematical Oncology presents biologically well-motivated and mathematically tractable models that facilitate both a deep understanding of cancer biology and better cancer treatment designs. It covers the medical and biological background of the diseases, modeling issues, and existing methods and their limitations. The authors introduce mathematical and programming tools, along with analytical and numerical studies of the models. They also develop new mathematical tools and look to future improvements on dynamical models. After introducing the general theory of medicine and exploring how mathematics can be essential in its understanding, the text describes well-known, practical, and insightful mathematical models of avascular tumor growth and mathematically tractable treatment models based on ordinary differential equations. It continues the topic of avascular tumor growth in the context of partial differential equation models by incorporating the spatial structure and physiological structure, such as cell size. The book then focuses on the recent active multi-scale modeling efforts on prostate cancer growth and treatment dynamics. It also examines more mechanistically formulated models, including cell quota-based population growth models, with applications to real tumors and validation using clinical data. The remainder of the text presents abundant additional historical, biological, and medical background materials for advanced and specific treatment modeling efforts. Extensively classroom-tested in undergraduate and graduate courses, this self-contained book allows instructors to emphasize specific topics relevant to clinical cancer biology and treatment. It can be used in a variety of ways, including a single-semester undergraduate course, a more ambitious graduate course, or a full-year sequence on mathematical oncology.

This collection of papers offers a broad synopsis of state-of-the-art mathematical methods used in modeling the interaction between tumors and the immune system. These papers were presented at the four-day workshop on Mathematical Models of Tumor-Immune System Dynamics held in Sydney, Australia from January 7th to January 10th, 2013. The workshop brought together applied mathematicians, biologists, and clinicians actively working in the field of cancer immunology to share their current research and to increase awareness of the innovative mathematical tools that are applicable to the growing field of cancer immunology. Recent progress in cancer immunology and advances in immunotherapy suggest that the immune system plays a fundamental role in host defense against tumors and could be utilized to prevent or cure cancer. Although theoretical and experimental studies of tumor-immune system dynamics have a long history, there are still many unanswered questions about the mechanisms that govern the interaction between the immune system and a growing tumor. The multidimensional nature of these complex interactions requires a cross-disciplinary approach to capture more realistic dynamics of the essential biology. The papers presented in this volume explore these issues and the results will be of interest to graduate students and researchers in a variety of fields within mathematical and biological sciences.

The book aims to provide an introduction to mathematical models that describe the dynamics of tumor growth and the evolution of tumor cells. It can be used as a textbook for advanced undergraduate or graduate courses, and also serves as a reference book for researchers. The book has a strong evolutionary component and reflects the viewpoint that cancer can be understood rationally through a combination of mathematical and biological tools. It can be used both by mathematicians and biologists. Mathematically, the book starts with relatively simple ordinary differential equation models, and subsequently explores more complex stochastic and spatial models. Biologically, the book starts with explorations of the basic dynamics of tumor growth, including competitive interactions among cells, and subsequently moves on to the evolutionary dynamics of cancer cells, including scenarios of cancer initiation, progression, and treatment. The book finishes with a discussion of advanced topics, which describe how some of the mathematical concepts can be used to gain insights into a variety of questions, such as epigenetics, telomeres, gene therapy, and social interactions of cancer cells. Contents:Teaching GuideCancer and Somatic EvolutionMathematical Modeling of TumorigenesisBasic Growth Dynamics and Deterministic Models:Single Species GrowthTwo-Species Competition DynamicsCompetition Between Genetically Stable and Unstable CellsChromosomal Instability and Tumor GrowthAngiogenesis Inhibitors, Promoters, and Spatial GrowthEvolutionary Dynamics and Stochastic Models:Evolutionary Dynamics of Tumor Initiation Through Oncogenes: The Gain-of-Function ModelEvolutionary Dynamics of Tumor Initiation Through Tumor-Suppressor Genes: The Loss-of-Function Model and Stochastic TunnelingMicrosatellite and Chromosomal Instability in Sporadic and Familial Colorectal CancersEvolutionary Dynamics in Hierarchical PopulationsSpatial Evolutionary Dynamics of Tumor InitiationComplex Tumor Dynamics in SpaceStochastic Modeling of Cellular Growth, Treatment, and Resistance GenerationEvolutionary Dynamics of Drug Resistance in Chronic Myeloid LeukemiaAdvanced Topics:Evolutionary Dynamics of Stem-Cell Driven Tumor GrowthTumor Growth Kinetics and Disease ProgressionEpigenetic Changes and the Rate of DNA MethylationTelomeres and Cancer ProtectionGene Therapy and Oncolytic Virus TherapyImmune Responses, Tumor Growth, and TherapiesTowards Higher Complexities: Social Interactions Readership: Researchers in mathematical biology, mathematical modeling, biology, mathematical oncology. Keywords:Mathematical Oncology;Dynamics;Evolution;Evolutionary Dynamics;Cancer;Mathematical Models;Somatic Evolution;TeachingKey Features:Both a reference book for the topic, and provides material for undergraduate and graduate coursesTries to bridge the divide between mathematicians and biologists, which is also reflected in the backgrounds of the two authorsShows how mathematical concepts can be translated into experimentally and clinically useful insightsRooted in evolutionary biology, the book handles this very complex phenomenon in an intuitive and mathematically elegant wayContains problems and research projects for each topic10 pages of figures in color

Mathematical modeling, analysis and simulation are set to play crucial roles in explaining tumor behavior, and the uncontrolled growth of cancer cells over multiple time and spatial scales. This book, the first to integrate state-of-the-art numerical techniques with experimental data, provides an in-depth assessment of tumor cell modeling at multiple scales. The first part of the text presents a detailed biological background with an examination of single-phase and multi-phase continuum tumor modeling, discrete cell modeling, and hybrid continuum-discrete modeling. In the final two chapters, the authors guide the reader through problem-based illustrations and case studies of brain and breast cancer, to demonstrate the future potential of modeling in cancer research. This book has wide interdisciplinary appeal and is a valuable resource for mathematical biologists, biomedical engineers and clinical cancer research communities wishing to understand this emerging field.

Introduction to Mathematical Oncology presents biologically well-motivated and mathematically tractable models that facilitate both a deep understanding of cancer biology and better cancer treatment designs. It covers the medical and biological background of the diseases, modeling issues, and existing methods and their limitations. The authors introduce mathematical and programming tools, along with analytical and numerical studies of the models. They also develop new mathematical tools and look to future improvements on dynamical models. After introducing the general theory of medicine and exploring how mathematics can be essential in its understanding, the text describes well-known, practical, and insightful mathematical models of avascular tumor growth and mathematically tractable treatment models based on ordinary differential equations. It continues the topic of avascular tumor growth in the context of partial differential equation models by incorporating the spatial structure and physiological structure, such as cell size. The book then focuses on the recent active multi-scale modeling efforts on prostate cancer growth and treatment dynamics. It also examines more mechanistically formulated models, including cell quota-based population growth models, with applications to real tumors and validation using clinical data. The remainder of the text presents abundant additional historical, biological, and medical background materials for advanced and specific treatment modeling efforts. Extensively classroom-tested in undergraduate and graduate courses, this self-contained book allows instructors to emphasize specific topics relevant to clinical cancer biology and treatment. It can be used in a variety of ways, including a single-semester undergraduate course, a more ambitious graduate course, or a full-year sequence on mathematical oncology.

This book presents original papers reflecting topics featured at the international symposium entitled “Fusion of Mathematics and Biology” and organized by the editor of the book. The symposium, held in October 2020 at Osaka University in Japan, was the core event for the final year of the research project entitled “Establishing International Research Networks of Mathematical Oncology.” The project had been carried out since April 2015 as part of the Core-to-Core Program of Japan Society for the Promotion of Science (JSPS). In this book, the editor presents collaborative research from prestigious organizations in France, the UK, and the USA. By utilizing their individual strengths and realizing the fusion of life science and mathematical science, the project achieved a combination of mathematical analysis, verification by biomedical experiments, and statistical analysis of chemical databases. Mathematics is sometimes regarded as a universal language. It is a valuable property that everyone can understand beyond the boundaries of culture, religion, and language. This unifying force of mathematics also applies to the various fields of science. Mathematical oncology has two aspects, i.e., data science and mathematical modeling, and definitely helps in the prediction and control of biological phenomena observed in cancer evolution. The topics addressed in this book represent several methods of applying mathematical modeling to scientific problems in the natural sciences. Furthermore, novel reviews are included that may motivate many mathematicians to become interested in biological research.

Physical oncology has the potential to revolutionize cancer research and treatment. The fundamental rationale behind this approach is that physical processes, such as transport mechanisms for drug molecules within tissue and forces exchanged by cancer cells with tissue, may play an equally important role as biological processes in influencing progression and treatment outcome. This book introduces the emerging field of physical oncology to a general audience, with a focus on recent breakthroughs that help in the design and discovery of more effective cancer treatments. It describes how novel mathematical models of physical transport processes incorporate patient tissue and imaging data routinely produced in the clinic to predict the efficacy of many cancer treatment approaches, including chemotherapy and radiation therapy. By helping to identify which therapies would be most beneficial for an individual patient, and quantifying their effects prior to actual implementation in the clinic, physical oncology allows doctors to design treatment regimens customized to each patient’s clinical needs, significantly altering the current clinical approach to cancer treatment and improving the outcomes for patients.