Antiangiogenic Cancer Therapy Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page i 20.6.2007 3:29pm Compositor Name: DeShanthi Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page ii 20.6.2007 3:29pm Compositor Name: DeShanthi CRC Press is an imprint of the Taylor & Francis Group, an informa business Boca Raton London New York Antiangiogenic Cancer Therapy Edited by Darren W. Davis Roy S. Herbst James L. Abbruzzese Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page iii 20.6.2007 3:29pm Compositor Name: DeShanthi CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2008 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-13: 978-0-8493-2799-5 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. 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Library of Congress Cataloging-in-Publication Data Antiangiogenic cancer therapy / edited by Darren W. Davis and Roy S. Herbst, James L. Abbruzzese p. ; cm. Includes bibliographical references and index. ISBN-13: 978-0-8493-2799-5 (hardcover) ISBN-10: 0-8493-2799-7 (hardcover) 1. Neovascularization inhibitors. I. Davis, Darren W., 1971- II. Herbst, Roy. III. Abbruzzese, James L. IV. Title. [DNLM: 1. Neoplasms--drug therapy. 2. Angiogenesis Inhibitors--therapeutic use. QZ 267 A6283 2007] RC271.N46.A585 2007 616.99’4061--dc22 2007000598 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page iv 20.6.2007 3:29pm Compositor Name: DeShanthi 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 neovasculari- zation (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 observa- tion 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 angiogenesis- dependent 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 meta- static 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 bevacizu- mab 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 clini- cians, 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 experi- mental 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. Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page v 20.6.2007 3:29pm Compositor Name: DeShanthi 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. ABSTRACT Antiangiogenic Cancer Therapy brings together basic scientists and oncologists to provide the most authoritative, up-to-date, and encyclopedic volume currently available on this subject. Part I of this book introduces a series of concepts and topics regarding the role of angiogenesis in cancer. These topics include strategies to prolong the nonangiogenic dormant state of human tumors, molecular mechanisms and cellular regulation of angiogenesis in solid tumors and hematologic malignancies, and the regulation of angiogenesis by the tumor microenviron- ment. Part II of the book covers specific molecular targets for inhibiting angiogenesis in cancer therapy. Part III discusses clinical trial design and translational research approaches essential for identifying and developing effective angiogenesis inhibitors. These discussions include noninvasive imaging methods and direct analysis of tissue biopsies. Part IV of the book covers antiangiogenic treatment for specific cancer types. These chapters are introduced by state-of-the-art discussions outlining the current understanding of the molecular biology of each cancer type followed by discussions that examine strategies for targeting angiogenesis. Organizing the chapters in this format will allow the reader to easily find the information necessary to understand the fundamental concepts of angiogenesis and the complexities associated with targeting angiogenesis for specific types of cancer. This book will serve to provide information useful to scientists and physicians engaged in the study and development of antiangiogenic agents, as well as medical professionals, medical and graduate students, and allied health professionals interested in learning more about the biology and clinical use of angiogenesis inhibitors. Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page vi 20.6.2007 3:29pm Compositor Name: DeShanthi Editors Dr Darren W. Davis is president and chief executive officer of ApoCell, Inc., an innovative molecular diagnostic company located near the world famous Texas Medical Center, Houston, Texas. Dr Davis has a BS in biochemical and biophysical sciences and earned his PhD in cancer biology and toxicology at the University of Texas Graduate School of Biomedical Sciences and the University of Texas M.D. Anderson Cancer Center in Houston, Texas. Dr Davis continued his postgraduate training at M.D. Anderson Cancer Center where he developed several methods to analyze the effects of molecular-targeted therapies, including angiogenesis inhibitors, to support clinical drug development. He was shortly promoted to junior faculty and served as one of six investigators of the Goodwin Molecular Monitoring Laboratory for clinical biomarker development, Department of Translational Research, before founding ApoCell in 2004, an M.D. Anderson Cancer Center spin-off company. Dr Davis serves as the principal investigator for numerous biological correlative studies to support clinical trials. His research interests center on molecular mechanisms, apoptosis, and signal transduction of molecular-targeted therapies. Dr Davis has evaluated the pharmaco- dynamic effects of both conventional and drug-targeted therapies in a wide variety of animal and clinical specimens. Dr Davis has frequently been invited to speak at both national and international conferences and scientific advisory meetings. Dr Davis serves as a consultant for both basic scientists and clinicians and helps identify and select critical end points for clinical trials with leading pharmaceutical companies. Dr Davis is author or coauthor of more than 50 publications, including peer-reviewed journal articles, abstracts, book chapters, and has served as an editor. He has contributed his work to many prominent journals, such as, Journal of Experimental Medicine, Cancer Research, Journal of Clinical Oncology, Clinical Cancer Research, Lung Cancer, Cancer, and Seminars in Oncology. His abstracts have been presented at the annual meetings of the American Society of Clinical Oncology, the American Associ- ation for Cancer Research, and the European Organization for Research and Treatment of Cancer. Dr Davis is the inventor of four pending patents. Dr Roy S. Herbst is professor and chief of the Section of Thoracic Medical Oncology in the Department of Thoracic=Head and Neck Medical Oncology, at the University of Texas M.D. Anderson Cancer Center in Houston, Texas. He also serves as professor in the Department of Cancer Biology and codirector of the Phase I working group. Dr Herbst earned his MD at Cornell University Medical College and his PhD in molecular cell biology at the Rockefeller University in New York City, New York. His postgraduate training included an internship and residency in medicine at Brigham and Women’s Hospital in Boston, and a chief residency at West Roxbury Veterans Administration Hospital in Dedham, Massachusetts. His clinical fellowships in medicine and hematology were completed at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, respectively. Subsequently, Dr Herbst completed the MS degree in clinical translational research at Harvard University in Cambridge, Massachusetts. Dr Herbst serves as the principal investigator for numerous trials and has conducted research primarily in the treatment of lung cancer, head and neck cancer, and Phase I studies. His Laboratory and Clinical work has focused on the clinical development of molecular-targeted therapies. Dr Herbst has frequently been invited to speak at both national and international conferences. Dr Herbst is author or coauthor of more than 200 publications, including peer-reviewed journal articles, abstracts, and book chapters. He has contributed his work to many prominent journals, such as Journal of Clinical Oncology, Clinical Cancer Research, Clinical Lung Cancer, Lung Cancer, Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page vii 20.6.2007 3:29pm Compositor Name: DeShanthi Cancer, Annals of Oncology, and Seminars in Oncology. His abstracts have been presented at the annual meetings of the American Society of Clinical Oncology, the American Association for Cancer Research, the World Conference on Lung Cancer, the Society of Nuclear Medicine Conference, and the European Organization for Research and Treatment of Cancer. Dr Herbst is an active member of the American Society of Clinical Oncology, the American Association for Cancer Research, the International Association for the Study of Lung Cancer, the Radiation Therapy Oncology Group, and the Southwest Oncology Group Lung Committee. He served as chairman of the American Society of Clinical Oncology—Lung Cancer Program Subcommittee (2001–2002), vice chairman of the Radiation Therapy Oncology Group—Lung Committee, vice chairman of the Southwest Oncology Group—Lung Committee, guest planner of the Annual Meeting Education Program (2003), chairman of the International Association for the Study of Lung Cancer—Targeted Therapy Division of the Translational Research and Tar- geted Therapy Subcommittee (2003 and 2005), and chairman of the American Society of Clinical Oncology—Cancer Communication Committee (2005–2006). Notably Dr Herbst is the recipient of the American Society of Clinical Oncology Young Investigator Award, the American Society of Clinical Oncology Career Development Award (1999, 2000), and the M.D. Anderson Cancer Center Physician Scientist Program Award (1999–2002). Dr James L. Abbruzzese is the M.G. and Lillie A. Johnson chair for cancer treatment and research and chairman of the Department of Gastrointestinal Medical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston, Texas. Dr Abbruzzese is a member of numerous scientific advisory boards including the external scientific advisory board for the University of Massachusetts, the Arizona Cancer Center, the Lustgarten Foundation for Pancreatic Cancer Research, and the Pancreatic Cancer Action Network. Born in Hartford, Connecticut, Dr Abbruzzese graduated medical school with honors from the University of Chicago, Pritzker School of Medicine, Chicago, Illinois. He completed residency in internal medicine at the Johns Hopkins Hospital in Baltimore, Maryland, and fellowship in medical oncology at the Dana-Farber Cancer Center, Harvard Medical School in Boston, Massachusetts. He is married and has one child. Dr Abbruzzese has published over 200 peer-reviewed articles, numerous chapters, and reviews. In 2004, he coedited a book entitled Gastrointestinal Oncology published by Oxford University Press. His research group was recently awarded a SPORE in pancreatic cancer and U54 grant on angiogenesis. In 2001, Dr Abbruzzese served as a cochair of the American Association for Cancer Research Program Committee. He is a member of the American Association for Cancer Research Fellowships Committee, the American Society of Clinical Oncology Grant Awards and Nominating Committees, and has many other board memberships. Dr Abbruzzese is a deputy editor of Clinical Cancer Research and member of several other editorial boards in the past including the Journal of Clinical Oncology. His clinical interests center on pancreatic cancer, new drug development, and noninvasive assessment of anticancer drug effects. Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page viii 20.6.2007 3:29pm Compositor Name: DeShanthi Contributors Abebe Akalu Departments of Radiation Oncology and Cell Biology New York University School of Medicine Cancer Institute New York, New York Kenneth C. Anderson Jerome Lipper Multiple Myeloma Center Department of Medical Oncology Dana-Farber Cancer Institute and Harvard Medical School Boston, Massachusetts Khalid Bajou Division of Hematology–Oncology Departments of Pediatrics and Biochemistry and Molecular Biology University of Southern California Keck School of Medicine and Saban Research Institute of Children’s Hospital Los Angeles, California Cheryl H. Baker Department of Biomedical Sciences University of Central Florida Orlando, Florida and Cancer Research Institute M.D. Anderson Cancer Center–Orlando Orlando, Florida Pablo M. Bedano Division of Hematology–Oncology Indiana University School of Medicine Indianapolis, Indiana Peter C. Brooks Departments of Radiation Oncology and Cell Biology New York University School of Medicine Cancer Institute New York, New York Thomas R. Burkard Institute for Genomics and Bioinformatics and Christian Doppler Laboratory for Genomics and Bioinformatics Graz University of Technology Graz, Austria and Research Institute of Molecular Pathology Vienna, Austria David J. Chaplin Oxigene, Inc. Waltham, Massachusetts Dharminder Chauhan Jerome Lipper Multiple Myeloma Center Department of Medical Oncology Dana-Farber Cancer Institute and Harvard Medical School Boston, Massachusetts Ramzi N. Dagher Center for Drug Evaluation and Research U.S. Food and Drug Administration Silver Spring, Maryland Angus G. Dalgleish Division of Oncology Cell and Molecular Sciences St. Georges University of London London, United Kingdom Darren W. Davis ApoCell, Inc. Houston, Texas S. Davis Regeneron Pharmaceuticals, Inc. Tarrytown, New York Davis/Antiangiogenic Cancer Therapy 2799_C000 Final Proof page ix 20.6.2007 3:29pm Compositor Name: DeShanthi