Antiangiogenic Cancer Therapy PDF

Preface

In recent years, tremendous progress has been made in our understanding of molecular mechanisms and cellular regulation of angiogenesis in cancer. Despite this progress, clinical development of angiogenesis inhibitors for the treatment of cancer remains challenging. Given that solid tumors account for more than 85% of cancer mortality, and tumor growth and metastasis are dependent on blood vessels, targeting tumor angiogenesis is one of the most widely pursued therapeutic strategies today. Approaches to target angiogenesis in cancer include destroying the existing vasculature (antivascular) and inhibiting neovascularization (antiangiogenic). We hope that Antiangiogenic Cancer Therapy will stimulate the rapid translation and dissemination of basic science discoveries into novel clinical strategies that will provide more effective antiangiogenic therapies for cancer.

Antiangiogenic Cancer Therapy was made possible as a result of a key scientific observation made more than 40 years ago, when Drs Folkman and Becker observed that tumor growth in isolated perfused organs was limited in the absence of tumor vascularization. However, it was arguably Folkman's hypothesis that tumor growth is angiogenesisdependent in 1971 that led to the notion that angiogenesis could be a relevant target for tumor therapy. Twenty years later, the successful treatment of an angiogenesis-dependent pulmonary hemangioma (a benign tumor) with interferon a-2a enabled physicians and scientists to recognize the potential therapeutic benefit of targeting angiogenesis for cancer therapy. Indeed, in 1999 the development of antiangiogenic therapies for cancer became a top priority of the National Cancer Institute. The first angiogenesis inhibitor, bevacizumab, was approved by the Food and Drug Administration in 2004 for the treatment of metastatic carcinoma of the colon or rectum. Subsequently in 2006, bevacizumab was approved for first-line treatment of patients with advanced nonsquamous nonsmall cell lung cancer.

Although information in the field of angiogenesis is rapidly expanding, our capacity to efficiently process and implement this knowledge has not kept pace. For example, no randomized Phase III trial has demonstrated a survival benefit with currently available antiangiogenic agents when used as a monotherapy. However, the combination of bevacizumab with cytotoxic regimens has led to survival benefit in previously untreated colorectal, lung, and breast cancer, and in previously treated colorectal cancer patients. These results raise important questions about the complexity and use of angiogenesis inhibitors in clinical practice. The thesis of Antiangiogenic Cancer Therapy is that by understanding the molecular and cellular regulation of angiogenesis itself, we will be able to understand and implement the most optimal therapeutic strategies. This challenge creates an overwhelming task for clinicians, scientists, teachers, and authors. We have carefully considered what facts and concepts are essential elements to include in this book. An aim of this book is to integrate the fundamental concepts of angiogenesis with therapeutic strategies specific to various cancer types. Thus, although each chapter may stand alone, the scientific details within each chapter provide strength to the overall conceptual framework of the book.

We are deeply grateful to the many people who have helped us compose this book. The experts who contributed to each chapter are the most authoritative in their respective fields. However, their contributions would not be possible without many years of laborious experimental failures and successes by many investigators throughout the world. Therefore, we are also indebted to the many scientists whose contributions have led to remarkable scientific advances, which are cited within each chapter. Finally, we are thankful to the outstanding staff at Taylor & Francis who oversaw the final production of this book.

Since the initial discovery that tumors are angiogenesis-dependent was made four decades ago, this edition is a celebration of the remarkable scientific progress made during that time, and we hope an even better indication of the future to come.