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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.
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.
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.
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.
The war against cancer continues to take its toll on society, even after many decades of focused, intensive research into its origins and cures. Increasingly, efforts are being made to incorporate physical sciences and mathematical approaches in this battle. The term "integrated mathematical oncology" has been coined, which serves to unify the biological and quantitative sciences to bring a fresh perspective to cancer research. In this vein, mathematical modeling is beginning to serve many purposes, from providing a theoretical framework for biological hypothesis testing, to producing data-driven predictions of future disease behavior, to ultimately laying a foundation for personalized medicine. Glioblastoma is an aggressive primary brain tumor which presents a particularly significant opportunity for personalized medicine. Glioblastoma is a diffusely invading cancer which blurs the lines between normal brain and malignant tumor. The disease is formally named glioblastoma multiforme (GBM), to emphasize the pathogenic and morphologic heterogeneity of the disease. Despite this heterogeneity, treatment options are limited and somewhat algorithmic. Nearly all patients diagnosed with GBM will receive radiation and chemo-therapy following surgery. The diverse nature of the disease combined with a 12--14 month prognosis and a "one size fits all" approach to treatment, leads to a unique opportunity for integrated mathematical oncology in the form of patient-specific modeling. I present studies and analysis of mathematical models of radiation therapy-induced DNA damage and repair kinetics, as well as a clinically targeted mathematical model of glioblastoma growth and invasion which incorporates the effects of radiation therapy that links to the concept of personalized medicine by way of estimating patient-specific parameters in a mechanistic model. Specifically, I present analytic solutions for a nonlinear, two-compartment ODE model of radiation-induced DNA damage and repair, which illustrates orders of magnitude differences between the linearized solution used pervasively in the literature, and the analytic solution to the fully nonlinear model. Further, data-driven parameterization of the DNA damage and repair model reveals superior model prediction and parameter stability across a wide range of experimental conditions compared to current model paradigms. I also present the implications of a patient-specific calibration of a reaction-diffusion model for glioblastoma growth. This patient-specific model is expanded to include delivery and temporally delayed response to radiation therapy to yield a predictive relationship between the net rate of proliferation and radiation sensitivity. The patient-specific radiation therapy model is expanded to include spatially and temporally defined treatment delivery and hypoxia-mediated treatment resistance. This extension advances the patient-specific radiation response model into 3D, improves model accuracy, and demonstrates a multifaceted application of patient-specific mathematical modeling for translation to the clinical setting.
This book constitutes the refereed proceedings of the Third International Symposium on Mathematical and Computational Oncology, ISMCO 2021, held in October 2021. Due to COVID-19 pandemic the conference was held virtually. The 3 full papers and 4 short papers presented were carefully reviewed and selected from 20 submissions. The papers are organized in topical sections named: statistical and machine learning methods for cancer research; mathematical modeling for cancer research; spatio-temporal tumor modeling and simulation; general cancer computational biology; mathematical modeling for cancer research; computational methods for anticancer drug development.
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.
The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on cell biology and a chapter on control theory have been included. Those readers who have had some exposure to biology may prefer to omit Chapter I (Cell Biology) and only use it as a reference when required. However, few biologists have been exposed to control theory. Chapter 7 provides a short, coherent and comprehensible presentation of this subject. The concepts of control theory are necessary for a full understanding of Chapters 8 and 9.
This book constitutes the refereed proceedings of the First International Symposium on Mathematical and Computational Oncology, ISMCO'2019, held in Lake Tahoe, NV, USA, in October 2019. The 7 full papers presented were carefully reviewed and selected from 30 submissions. The papers are organized in topical sections named: Tumor evolvability and intra-tumor heterogeneity; Imaging and scientific visualization for cancer research; Statistical methods and data mining for cancer research (SMDM); Spatio-temporal tumor modeling and simulation (STTMS).
This book constitutes the refereed proceedings of the Third International Symposium on Mathematical and Computational Oncology, ISMCO 2021, held in October 2021. Due to COVID-19 pandemic the conference was held virtually. The 3 full papers and 4 short papers presented were carefully reviewed and selected from 20 submissions. The papers are organized in topical sections named: statistical and machine learning methods for cancer research; mathematical modeling for cancer research; spatio-temporal tumor modeling and simulation; general cancer computational biology; mathematical modeling for cancer research; computational methods for anticancer drug development.