Tumor Vascularization

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

First Published in 1979, this book offers a full, insight into the relationship between malignant tumors and blood flow. Carefully compiled and filled with a vast repertoire of notes, diagrams, and references this book serves as a useful reference for students of oncology, and other practitioners in their respective fields.

In 1971, J. Folkman published in the “New England Journal of Medicine” a hypothesis that tumor growth is angiogenesis-dependent. Folkman introduced the concept that tumors probably secrete diffusible molecules that could stimulate the growth of new blood vessels toward the tumor and that the resulting tumor neovascularization could conceivably be prevented or interrupted by angiogenesis inhibitors. Solid and haematological tumors consist of an avascular and a subsequent vascular phase. Assuming that this depends on the release of angiogenic factors, acquisition of angiogenic capability can be seen as an expression of progression from neoplastic transformation to tumor growth and metastasis. Beginning in the 1980’s, the biopharmaceutical industry began exploiting the field of antiangiogenesis for creating new therapeutic compounds for modulating new blood vessels in tumor growth. In 2004, Avastin (Bevacizumab), a humanized anti-VEGF monoclonal antibody, was the first angiogenesis inhibitor approved by the Food and Drug Administration for the treatment of colorectal cancer. At present, it has been estimated that over 20,000 cancer patients worldwide have received experimental form of antiangiogenic therapy. This book offers a historical account of the relevant literature. It also emphasizes the crucial and paradigmatic role of angiogenesis as a biological process and the significance of antiangiogenic approach for the treatment of tumors.

Tumor angiogenesis is the main process responsible for the formation of new blood vessels that promote tumor growth and metastasis. This process is driven by potent pro-angiogenic factors that are predominant in the tumor environment and are produced by both malignant cells and the host cells recruited to the tumor site. Tumor environment is characterized by the imbalance between pro-angiogenic and anti-angiogenic factors, which drives the construction of numerous but structurally defective vessels. These poorly perfused and abnormal vessels significantly contribute to the tumor pathology not only by supporting the expansion of the tumor mass but also by promoting chronic inflammation, enhancing thrombosis, impeding drug delivery, and disseminating tumor cells. These problems associated with tumor vasculature continue to attract great attention of scientists and clinicians interested in advancing the understanding of tumor biology and development of new drugs. This book complies a series of reviews that cover a broad spectrum of current topics related to the pathology of tumor blood vessels including mechanisms inducing new vessels, identification of new targets for inhibition of tumor angiogenesis, and potential clinical use of known and novel anti-angiogenic therapies. The book provides an update on tumor angiogenesis that could be useful for oncologists, cancer researchers and biologists with interests in vascular and endothelial cell behavior in the context of cancer.

The emphasis of this book is on mechanisms and pathways regulating the expression and actions of classical and novel tumor angiogenesis regulators. The contributors discuss their underlying biology as well as anti-angiogenic drugs currently in use to fight different cancers. The book provides an insight on how factors such as obesity, diabetes, and

Tumor angiogenesis is one of the most prominent mechanisms driving tumor development and progression. This book is written by internationally renowned experts. Part 1 describes the basic mechanisms. Tumor-angiogenic signaling pathways are presented as new potential targets for anti-angiogenic therapy. Part 2 reviews the efforts made to validate new targets and to show efficacy in animals. Part 3 is devoted to the clinical development of the novel anti-angiogenic drugs and their use in clinical practice.

Angiogenesis (formation of new vessels from pre-existing ones) is a crucial early event in the process of tumor development. New vessels supply the tumor with nutrients that are needed for further local growth and enable distant metastases (Folkman 1995). Judah Folkman (1971) highlighted the potential therapeutic imp- cations of tumor angiogenesis. He hypothesized that if tumor angiogenesis is inhibited, then tumor growth and metastasis will be impaired greatly or even impossible. The subsequent quest for endogenous and exogenous inhibitors of angiogenesis has yielded a variety of promising therapeutic agents that block one or more angiogenic pathways, a few of which have been approved by the FDA (e. g. , bevacizumab, sorafenib, sunitinib) for use as single agents or in combination with chemotherapy in specific populations of cancer patients (Sessa et al. 2008). There has also been a dramatic expansion in the exploration of novel anti-angiogenic agents pre-clinically and in clinical trials (Ferrara 2002). Some of the most promising data comes from the development of agents that inhibit one of the key growth factors involved in tumor angiogenesis – vascular endothelial growth factor (VEGF) (Ferrara et al. 2003). Bevacizumab is a monoclonal antibody against VEGF that was the first an- angiogenic agent that improved significantly the overall survival of patients with colorectal and non-squamous non-small cell lung cancer (Ferrara et al. 2005). Various agents that target tumor angiogenesis are currently under investigation in different cancer types in many clinical trials (Ferrara and Kerbel 2005).

Themen dieses Bandes sind die molekularen Mechanismen der Tumor-Angiogenese, die Suche nach einschlägigen Targets für die Wirkstoffforschung und die Entwicklung von Kombinationstherapien mit bereits existierenden Ansätzen. Die ideale Informationsquelle für Studenten, Ärzte und Forscher in der Pharmaindustrie!

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