Modeling Tumor Vasculature

To profoundly understand biology and harness its intricacies for human benefit and the mitigation of human harm requires cross-disciplinary approaches that incorporate sophisticated computational and mathematical modeling techniques. These integrative strategies are essential to achieve rapid and significant progress in issues, in health and disease, which span molecular, cellular and tissue levels. The use of mathematical models to describe various aspects of tumor growth has a very long history, dating back over six decades. Recently, however, experimental and computational advances have improved our in the understanding of how processes act at multiple scales to mediate the development of tumor vasculature and drive the advancement of cancer. This book will showcase the development and utilization of new computational and mathematical approaches to address multiscale challenges associated with tumor vascular development. In Part I: Cell Signaling and Molecular Aspects of Tumor Blood Vessel Formation, it will be come clear that mathematical modeling can help to biochemically and biomechanically phenotype one of the most important cell types involved in cancer progression: vascular endothelial cells. When subverted by the tumor modulated environment, vascular endothelial cells form a new vascular supply capable of nourishing and translocating cancer cells to other tissues. The models in Part I illustrate the importance of quantitative approaches for gaining a deeper understanding of how normal and abnormal aspects of signal integration culminate in the cell proliferation, migration, and survival decisions that result in pathological tumor angiogenesis. The focus of Part II is the angiogenesis cascade and all of its complexities. Successful angiogenesis is mediated by the intricate interplay between biochemical and biomechanical mechanisms, including cell-cell and cell-matrix interactions, cell surface receptor binding, and intracellular signal transduction. A major challenge facing the cancer research community is to integrate known information in a way that improves our understanding of the principal underpinnings driving tumor angiogenesis and that will advance efforts aimed at the development of new therapies for treating cancer. The chapters in Part II will highlight several mathematical and computational approaches for that can potentially address this challenge. While the first two thirds of the book’s chapters demonstrate how important insights can be gained by studying cell signaling and vascular morphology and function, the series of chapters in Part III: Whole Organ Modeling of Tumor Growth and Vasculature, will integrate vasculature development with tumor growth dynamics. These two processes strongly depend on one another in ways that can only be theoretically investigated by biophysical approaches that cut across several levels of biological organization and describe both the tumor and the developing vasculature as they co-evolve. The purpose of this edited volume is not to provide a comprehensive review of all modeling efforts that address tumor vascular modeling; instead, a variety of interesting and innovative mathematical modeling approaches for understanding the development and effects of tumor vasculature are highlighted in order to illustrate some of the emerging trends in the field.

Tumor Vascularization discusses the different types of growth of tumor blood vessels and their implications on research and healthcare. The book is divided into three parts: the first one, General Mechanisms, discusses different vessel growth mechanisms, such as sprouting angiogenesis, non-angiogenesis dependent growth, intussusceptive microvascular growth, vascular co-option and vasculogenic mimicry. The second and third parts, entitled Clinical Implications and Therapeutic Implications are dedicated to translating recent findings in this field to patient treatment and healthcare. This book is a valuable source for cancer researchers, oncologists, graduate students and members of the biomedical field who are interested in tumor progression and blood vessels. Explains new, non-orthodox concepts recently developed and related to the modality of growth of tumor blood vessels Provides information on the types of angiogenesis, non-angiogenesis dependent growth and vascular co-option, discussing both their similarities and differences Encompasses a discussion on clinical implications of tumor vascularization to translate research findings into treatment

This edited volume discusses the complexity of tumor microenvironments during cancer development, progression and treatment. Each chapter presents a different mathematical model designed to investigate the interactions between tumor cells and the surrounding stroma and stromal cells. The topics covered in this book include the quantitative image analysis of a tumor microenvironment, the microenvironmental barriers in oxygen and drug delivery to tumors, the development of tumor microenvironmental niches and sanctuaries, intravenous transport of the circulating tumor cells, the role of the tumor microenvironment in chemotherapeutic interventions, the interactions between tumor cells, the extracellular matrix, the interstitial fluid, and the immune and stromal cells. Mathematical models discussed here embrace both continuous and agent-based approaches, as well as mathematical frameworks of solid mechanics, fluid dynamics and optimal control theory. The topics in each chapter will be of interest to a biological community wishing to apply the mathematical methods to interpret their experimental data, and to a biomathematical audience interested in exploring how mathematical models can be used to address complex questions in cancer biology.

Vascular-Targeted Therapies in Oncology provides an interesting insight to the current status and future potential of vascular-disrupting approaches in cancer management. Emphasis is placed on target development, preclinical assessment, and the use of such targeted approaches in combination with conventional treatment regimens and the current clinical status of these therapies.

In Vivo Models to Study Angiogenesis provides the latest information and an overview of the most common assays for studying angiogenesis in vivo. Under physiological conditions, angiogenesis is tightly controlled, whereas increased production of angiogenic stimuli and/or reduced production of angiogenic inhibitors leads to abnormal neovascularization, such as occurs in cancer, chronic inflammatory disease, diabetic retinopathy, macular degeneration and cardiovascular disorders. Several genetic and epigenetic mechanisms are involved in the early development of the vascular system. This book presents the latest information from the extensive literature and research available. Evidence is now emerging that blood vessels themselves have the ability to provide instructive regulatory signals to surrounding non-vascular target cells during organ development. Thus, endothelial cell signaling is currently believed to promote fundamental cues for cell fate specification, embryo patterning, organ differentiation and postnatal tissue remodeling. Provides information on the most common assays to study angiogenesis in vivo Presents an ideal reference for those interested in angiogenesis as a normal and vital process in growth and development Covers wound healing, the formation of granulation tissue, and the transition of tumors from benign to malignant

Cancer is a complex disease process that spans multiple scales in space and time. Driven by cutting-edge mathematical and computational techniques, in silico biology provides powerful tools to investigate the mechanistic relationships of genes, cells, and tissues. It enables the creation of experimentally testable hypotheses, the integration of data across scales, and the prediction of tumor progression and treatment outcome (in silico oncology). Drawing on an interdisciplinary group of distinguished international experts, Multiscale Cancer Modeling discusses the scientific and technical expertise necessary to conduct innovative cancer modeling research across scales. It presents contributions from some of the top in silico modeling groups in the United States and Europe. The ultimate goal of multiscale modeling and simulation approaches is their use in clinical practice, such as supporting patient-specific treatment optimization. This volume covers state-of-the-art methods of multiscale cancer modeling and addresses the field’s potential as well as future challenges. It encourages collaborations among researchers in various disciplines to achieve breakthroughs in cancer modeling.

Understanding how cancer tumours develop and spread is vital for finding treatments and cures. Cancer Modelling and Simulation demonstrates how mathematical modelling and computer simulation techniques are used to discover and gain insight into the dynamics of tumour development and growth. It highlights the benefits of tumour modelling, such as discovering optimal tumour therapy schedules, identifying the most promising candidates for further clinical investigation, and reducing the number of animal experiments. By examining the analytical, mathematical, and biological aspects of tumour growth and modelling, the book provides a common language and knowledge for professionals in several disciplines.