Angiogenesis Modulations in Health and Disease

Angiogenesis Modulations in Health and Disease

Shaker A. Mousa Paul J. Davis Editors Angiogenesis Modulations in Health and Disease Practical Applications of Pro- and Anti-angiogenesis Targets

Editors Shaker A. Mousa The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences Rensselaer, NY, USA Paul J. Davis The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences Rensselaer, NY, USA ISBN 978-94-007-6466-8 ISBN 978-94-007-6467-5 (ebook) DOI 10.1007/978-94-007-6467-5 Springer Dordrecht Heidelberg New York London Library of Congress Control Number: 2013936733 Springer Science+Business Media Dordrecht 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

Contents Introduction... ix 1 Angiogenesis Assays: An Appraisal of Current Techniques... 1 Shaker A. Mousa and Paul J. Davis Part I Pro-angiogenesis Targets and Clinical Implications 2 Survey of Pro-angiogenesis Strategies... 15 Shaker A. Mousa 3 Angiogenesis Modulation by Arachidonic Acid-derived Lipids: Positive and Negative Regulators of Angiogenesis... 19 Robert C. Block, Murat Yalcin, Mathangi Srinivasan, Steve Georas, and Shaker A. Mousa 4 Pro-angiogenic Activity of Thyroid Hormone Analogues: Mechanisms, Physiology and Clinical Prospects... 29 Paul J. Davis, Faith B. Davis, Hung-Yun Lin, Mary K. Luidens, and Shaker A. Mousa 5 Actions of Steroids and Peptide Hormones on Angiogenesis... 47 Paul J. Davis, Shaker A. Mousa, Faith B. Davis, and Hung-Yun Lin 6 Role of Non-neuronal Nicotinic Acetylcholine Receptors in Angiogenesis Modulation... 55 Shaker A. Mousa, Hugo R. Arias, and Paul J. Davis 7 Catecholamine Neurotransmitters: An Angiogenic Switch in the Tumor Microenvironment... 77 Sujit Basu and Partha Sarathi Dasgupta 8 Impact of Nanotechnology on Therapeutic Angiogenesis... 87 Dhruba J. Bharali and Shaker A. Mousa v

vi Contents Part II Anti-angiogenesis Targets and Clinical Applications 9 Survey of Anti-angiogenesis Strategies... 95 Shaker A. Mousa 10 Tetraiodothyroacetic Acid (Tetrac), Nanotetrac and Anti-angiogenesis... 107 Paul J. Davis, Faith B. Davis, Mary K. Luidens, Hung-Yun Lin, and Shaker A. Mousa 11 Integrin Antagonists and Angiogenesis... 119 Shaker A. Mousa and Paul J. Davis 12 Anti-angiogenesis Therapy as an Adjunct to Chemotherapy in Oncology... 143 Shaker A. Mousa and Laila H. Anwar 13 Anti-VEGF Strategies in Ocular Angiogenesis-mediated Disorders, with Special Emphasis on Age-related Macular Degeneration... 157 Shaker A. Mousa 14 Application of Nanotechnology to Prevent Tumor Angiogenesis for Therapeutic Benefit... 173 Dhruba J. Bharali and Shaker A. Mousa 15 Biomarkers of Response and Resistance to Anti-angiogenic Treatment... 181 Dan G. Duda 16 Speculations on New Directions in Which Angiogenesis May Proceed... 199 Shaker A. Mousa and Paul J. Davis Index... 205

Contributors Laila H. Anwar Albany College of Pharmacy and Health Sciences, Albany, NY, USA Hugo R. Arias Department of Medical Education, College of Medicine, California North State University, Elk Grove, CA, USA Sujit Basu Department of Pathology and Arthur G. James Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA Dhruba J. Bharali The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA Robert C. Block Department of Public Health Sciences, Division of Cardiology, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Partha Sarathi Dasgupta Signal Transduction and Biogenic Amines Department, Chittaranjan National Cancer Institute, Kolkata, India Faith B. Davis The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA Paul J. Davis The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA Department of Medicine, Albany Medical Center, Albany, NY, USA Dan G. Duda Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Steve Georas Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA vii

viii Contributors Hung-Yun Lin Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan Mary K. Luidens Department of Medicine, Albany Medical College, Albany, NY, USA Shaker A. Mousa The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA Mathangi Srinivasan The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA Murat Yalcin Veterinary Medicine Faculty, Department of Physiology, Uludag University, Gorukle, Bursa, Turkey The Pharmaceutical Research Institute at Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA

Introduction Our intent in this textbook is to facilitate development of agents with clinical potential for modulating new blood vessel formation. We provide overviews of strategies in pro- and anti-angiogenesis, discuss certain classical and a number of recently emphasized targets in angiogenesis such as several integrins and we review the actions of classes of agents only recently appreciated to stimulate or inhibit angiogenesis. Discussed here is the impact of novel nanotechnology-based formulations of blood vessel-targeted drugs on the actions of these agents. We also review the assets and certain limitations of assays for angiogenesis and cover the challenging subject of biomarkers of new blood vessel formation. Finally, we speculate about new directions in which modulation of angiogenesis may proceed. We did not intend to provide an extensive overview of history and discovery in physiological and pathologic angiogenesis, but rather we present the current strategies in the modulation of angiogenesis in health and diseases. The feasibility of clinically important modulation of angiogenesis is a legacy of Dr. Judah Folkman s [1]. The concept moved through the three requisite phases of a newly appreciated truth that Schopenhauer described, namely, dismissal, then strenuous opposition and, finally, the declaration that the new truth was self-evident from the start. The motivation to identify steps in angiogenesis that could be manipulated was initially driven in Folkman and others by the desire to interrupt the vascularization of cancers. Potential anti-angiogenesis agents have emerged in concert with vascular growth factor discovery and the uncovering of steps in the molecular bases of growth factor action. A model case is that of vascular endothelial growth factor (VEGF), where antibodies or a trap have targeted VEGF, itself, and other agents have been directed at the VEGF receptor or at the kinases associated with the receptor. Vascular growth factors in addition to VEGF are of course now known to exist. Thus, it is not surprising that clinical effectiveness is variable from one type of cancer to another of a single anti-angiogenesis agent that targets a single apparent point of vulnerability in the mechanism of action of a single vascular growth factor. The concept of combining several anti-angiogenesis agents that target individual vascular growth factors VEGF, basic fibroblast growth factor (bfgf) and epidermal growth factor (EGF) in one therapeutic modality is attractive and, so far, impractical. ix

x Introduction That is, the individual agents are expensive to produce and the intellectual property is the province of different companies. An interesting strategy we discuss in several chapters in this text is looking at several endogenous human hormones that only recently have been seen to have angiogenesis-relevant actions that affect more than one vascular growth factor. The prototypical hormone in this context is an antiangiogenic iodothyronine analogue of thyroid hormone that acts via the cell surface receptor integrin avb3. Historically, the initial wave of therapeutic interest in anti-angiogenesis has been understandably followed by the search for pro-angiogenesis agents to be administered in settings of ischemia, preferably via local applications to avoid systemic spillover that might lead to increased risk of excessive vascular activation in patients at risk of cancer. The targets of course may be the same as those of anti-angiogenesis strategies where such targets in blood vessel cells have bidirectional capabilities. Several chapters in this textbook explore interesting and more recently appreciated pro-angiogenesis targets, including those subject to modulation by non-neuronal nicotinic acetylcholine receptors and certain receptors subject to modulation by arachidonic acid-derived lipids. The various pro-angiogenesis and anti-angiogenesis strategies described in this book and beyond might benefit greatly from novel nanoformulation approaches. The co-editors are very grateful to a substantial group of collaborators who contributed as co-authors and discussants to the realization of the textbook. The editorial contributions of Dr. Kelly Keating to each chapter were thoughtful and essential. We also appreciate the assistance of Ilse Hensen and Ganesan Divya at Springer in the completion of this project. Shaker A. Mousa, PhD, MBA, FACC, FACB Paul J. Davis, MD Reference 1. Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6(4):273 286