Vascular–Targeted Therapies in Oncology

Attacking a tumor’s supportive blood vessel network may offer novel means of improving cancer cure rates. The vasculature is critical to tumor development, survival, growth and metastatic spread. However, tumor blood vessels are abnormal, both morphologically and functionally, and display characteristics that distinguish them from normal vasculature. It is these inherent differences between blood vessels associated with tumors and those associated with normal tissues that provide a variety of unique targets for the design of novel therapeutics and treatment strategies highly selective for the cancer.
Vascular–disrupting strategies aim to cause a rapid and catastrophic shutdown in the established vessel networks of solid tumors. This arrests the blood flow and induces tumor cell death as a result of oxygen and nutrient deprivation and build up of waste products. Biological vascular–disrupting approaches include targeted gene therapy, antibodies to neovascular antigens and ligand–directed therapies targeting endothelial cell receptors and extracellular matrix proteins. Small molecule drug approaches have focused primarily on flavenoids and tubulin–binding agents. This book examines the fundamental bases of both these approaches.  Emphasis is placed on target development, preclinical assessment, use in combination with conventional treatment regimens and the current clinical status of these therapies.
This book is intended for cancer researchers and clinical oncologists.  Its goal is to review the potential of vascular–targeting strategies in cancer management and to foster an understanding of the key differences between these therapeutic approaches and conventional anticancer treatments. Though more research is required to establish the clinical efficacy and ideal application of vascular–disrupting strategies, this developing anticancer approach continues to generate great research interest and clinical optimi sm.

Spis treści:
Preface.
List of Contributors.
1 – Tumor Vasculature: a Target for Anticancer Therapies (Dietmar W. Siemann).
2 – Abnormal Microvasculature and Defective Microcirculatory Function in Solid Tumors (Peter Vaupel).
3 – The Role of Microvasculature in Metastasis Formation (Oliver Stöltzing, Lee M. Ellis).
4 – Development of Agents that Selectively Disrupt Tumor Vasculature: a Historical Perspective(David Chaplin, Sally A. Hill).
5 – Morphologic Manifestations of Vascular–Disrupting Agents in Preclinical Models (Mumtaz V. Rojiani, Amyn Rojiani).
6 – Molecular Recognition of the Colchicine Binding site as a Design Paradigm for the Discovery and Development of Vascular–Disrupting Agents (Kevin G. Pinney).
7 – Combined Modality Approaches Using Vascular–Disrupting Agents (Wenyin Shi, Michael R. Horsman, Dietmar W. Siemann).
8 – Vascular–Targeting Therapies and Hyperthermia (Michael R. Horsman, Rumi Murata).
9 – Flavones and Xanthenones as Vascular–Disrupting Agents (Bronwyn Siim, Bruce Baguley).
10 – Targeting Inside–Out Phospholipids on Tumor Blood Vessels in Pancreatic Cancer (Adam W. Beck, Rolf Brekken, Philip E. Thorpe, PhD).
11 – Cadherin Antagonists as Vascular–Targeting Agents (Orest Blaschuk, Tracey M. Rowlands).
12 – Alphastatin: a Pluripotent Inhibitor of Activated Endothelial Cells (Carolyn A. Staton, Claire Lewis)
13 – Cationic Lipid Complexes to Target Tumor Endothelium (Uwe Michaelis, Michael Teifel).
14 – Development of Vascular–Targeted Cancer Gene Therapy (Graeme J. Dougherty, Peter D. Davis, Shona T. Dougherty).
15 – Vascular–Disrupting Strategies Combined with Bacterial Spores Targeting Hypoxic Regions of Solid Tumors (G–One Ahn, J. Martin Brown).
16 – Imaging the Effects of Vascular–Targeting Agents (Susan M. Galbraith).
17 – Clinical Progress in Tumor Vascular–Disrupting Therapies (Andy Gaya, Gordon Rustin).
18 – Use of Vascular–Disrupting Agents in Non–Oncology Indications (Joseph C. Randall, Scott Young).


Okładka tylna:
Attacking a tumor’s supportive blood vessel network may offer novel means of improving cancer cure rates. The vasculature is critical to tumor development, survival, growth and metastatic spread. However, tumor blood vessels are abnormal, both morphologically and functionally, and display characteristics that distinguish them from normal vasculature. It is these inherent differences between blood vessels associated with tumors and those associated with normal tissues that provide a variety of unique targets for the design of novel therapeutics and treatment strategies highly selective for the cancer.
Vascular–disrupting strategies aim to cause a rapid and catastrophic shutdown in the established vessel networks of solid tumors. This arrests the blood flow and induces tumor cell death as a result of oxygen and nutrient deprivation and build up of waste products. Biological vascular–disrupting approaches include targeted gene therapy, antibodies to neovascular antigens and ligand–directed therapies targeting endothelial cell receptors and extracellular matrix proteins. Small molecule drug approaches have focused primarily on flavenoids and tubulin–binding agents. This book examines the fundamental bases of both these approaches.  Emphasis is placed on target development, preclinical assessment , use in combination with conventional treatment regimens and the current clinical status of these therapies.
This book is intended for cancer researchers and clinical oncologists.  Its goal is to review the potential of vascular–targeting strategies in cancer management and to foster an understanding of the key differences between these therapeutic approaches and conventional anticancer treatments. Though more research is required to establish the clinical efficacy and ideal application of vascular–disrupting strategies, this developing anticancer approach continues to generate great research interest and clinical optimism.