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ANTI-ANGIOGENESIS STRATEGIES IN CANCER THERAPIES Edited by SHAKER A. MOUSA The Pharmaceutical Research Institute Albany College of Pharmacy and Health Sciences Rensselaer, New York, United States PAUL J. DAVIS Department of Medicine, Albany Medical College Albany, New York, United States The Pharmaceutical Research Institute Albany College of Pharmacy and Health Sciences Rensselaer, New York, United States Amsterdam • Boston • Heidelberg • London New York • Oxford • Paris • San Diego San Francisco • Singapore • Sydney • Tokyo Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1800, San Diego, CA 92101-4495, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom Copyright © 2017 Elsevier Inc. All rights reserved. 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Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN: 978-0-12-802576-5 For information on all Academic Press publications visit our website at https://www.elsevier.com/ Publisher: Mica Haley Acquisition Editor: Kristine Jones Editorial Project Manager: Molly McLaughlin Production Project Manager: Julia Haynes Designer: Mark Rogers Typeset by Thomson Digital LIST OF CONTRIBUTORS Maii Abu Taleb The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States Dhruba J. Bharali The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States Noureldien H.E. Darwish The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States; Faculty of Medicine, Mansoura University, Mansoura, Egypt Paul J. Davis Department of Medicine, Albany Medical College, Albany, NY, United States; The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States Matthew Leinung Department of Medicine, Albany Medical College, Albany, NY, United States Shaker A. Mousa The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States Vandhana Muralidharan-Chari The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States Mehdi Rajabi The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States Domenico Ribatti Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School; National Cancer Institute “Giovanni Paolo II”, Bari, Italy Thangirala Sudha The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States Angelo Vacca Department of Biomedical Sciences, and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy Murat Yalcin The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States; Department of Physiology, V eterinary Medicine Faculty, Uludag University, Bursa, Turkey xi Introduction The requirement of aggressive cancers for rapidly growing blood vessels with unique structures [1,2] has rendered anti-angiogenesis [3] a highly attractive adjunct to standard chemotherapy or has led to its consideration as single-agent treatment. Anti-angiogenesis has been tested against a spectrum of solid tumors, including breast [4], ovary [5], prostate [6], hepatocellular carcinoma [7], lung cancers [8], and colon [9], among others. However, reviews of anti-angiogenic therapy in cancer conclude that this approach to-date has been disappointing [10–14]. Redundancy and upregulation of compensatory pro- angiogenesis pathways are a hallmark of tumor cell defenses in general and, not unexpectedly, our appreciation of the scope of mechanisms of tumor refractoriness to anti-angiogenesis continues to increase [15–18]. This has led to consideration of new directions in interventions in cancer-related blood vessel formation. Such new directions include combinations of anti-angiogenic agents [12], DNA-based immunotherapy directed at vasculature [19,20], anti-inflammation [21], anti-platelet therapy [22], and novel small molecules that serve to regulate the functions of multiple angiogenic factors [23,24]. Additionally, certain angiogenesis pathways, such as the integrin αvβ3 receptor complex might serve as a novel targeting strategy for imaging and targeted delivery for a nanoen- capsulated payload of various chemotherapies (Chapter 11). In this book, we summarize a number of mechanisms for limitations of anti-angiogenic interventions in cancer and have assembled reviews of a panel of strategies that may serve to improve effectiveness of anti-angiogenic interventions, alone, in cancer or in combination with chemotherapy. xiii xiv Introduction REFERENCES [1] Dvorak HF, Weaver VM, Tlsty TD, Bergers G. Tumor microenvironment and progression. J Surg Oncol 2011;103(6):468–74. [2] Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF. Heterogeneity of the tumor vasculature. Semin Thromb Hemost 2010;36(3):321–31. [3] Abdollahi A, Folkman J. Evading tumor evasion: current concepts and perspectives of anti-angiogenic cancer therapy. Drug Resist Updat 2010;13(1–2):16–28. [4] Lohmann AE, Chia S. Patients with metastatic breast cancer using bevacizumab as a treatment: is there still a role for it? Curr Treat Options Oncol 2012;13(2):249–62. [5] Eskander RN, Tewari KS. Incorporation of anti-angiogenesis therapy in the management of advanced ovarian carcinoma--mechanistics, review of phase III randomized clinical trials, and regulatory implications. Gynecol Oncol 2014;132(2):496–505. [6] Bilusic M, Wong YN. Anti-angiogenesis in prostate cancer: knocked down but not out. Asian J Androl 2014;16(3):372–7. [7] Sun H, Zhu MS, Wu WR, Shi XD, Xu LB. Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: the jury is still out. World J Hepatol 2014;6(12):830–5. [8] Ellis PM. Anti-angiogenesis in personalized therapy of lung cancer. Adv Exp Med Biol 2016;893:91–126. [9] Marien KM, Croons V, Martinet W, De Loof H, Ung C, Waelput W, Scherer SJ, Kockx MM, De Meyer GR. Predictive tissue biomarkers for bevacizumab-containing therapy in metastatic colorectal cancer: an up- date. Expert Rev Mol Diagn 2015;15(3):399–414. [10] Shojaei F. Anti-angiogenesis therapy in cancer: current challenges and fu- ture perspectives. Cancer Lett 2012;320(2):130–7. [11] Bellou S, Pentheroudakis G, Murphy C, Fotsis T. Anti-angiogenesis in cancer therapy: Hercules and hydra. Cancer Lett 2013;338(2):219–28. [12] Wang Z, Dabrosin C, Yin X, Fuster MM, Arreola A, Rathmell WK, Generali D, Nagaraju GP, El-Rayes B, Ribatti D, Chen YC, Honoki K, Fujii H, Georgakilas AG, Nowsheen S, Amedei A, Niccolai E, Amin A, Ashraf SS, Helferich B, Yang X, Guha G, Bhakta D, Ciriolo MR, Aqui- lano K, Chen S, Halicka D, Mohammed SI, Azmi AS, Bilsland A, Keith WN, Jensen LD. Broad targeting of angiogenesis for cancer prevention and therapy. Semin Cancer Biol 2015;35:S224–43. [13] Mitamura T, Gourley C, Sood AK. Prediction of anti-angiogenesis escape. Gynecol Oncol 2016;141(1):80–5. Introduction xv [14] Ye W. The complexity of translating anti-angiogenesis therapy from basic science to the clinic. Dev Cell 2016;37(2):114–25. [15] Giuliano S, Pages G. Mechanisms of resistance to anti-angiogenesis therapies. Biochimie 2013;95(6):1110–9. [16] Ribatti D. Tumor refractoriness to anti-VEGF therapy. Oncotarget 2016. [17] Huijbers EJ, van Beijnum JR, Thijssen VL, Sabrkhany S, Nowak-Sliwinska P, Griffioen AW. Role of the tumor stroma in resistance to anti-angiogenic therapy. Drug Resist Updat 2016;25:26–37. [18] Pinto MC, Sotomayor P, Carrasco-Avino G, Corvalan AH, Owen GI. Escaping antiangiogenic therapy: strategies employed by cancer cells. Int J Mol Sci 2016;17(9.). [19] Ugel S, Facciponte JG, De Sanctis F, Facciabene A. Targeting tumor vasculature: expanding the potential of DNA cancer vaccines. Cancer Immunol Immunother 2015;64(10):1339–48. [20] Wagner SC, Ichim TE, Ma H, Szymanski J, Perez JA, Lopez J, Bogin V, Patel AN, Marincola FM, Kesari S. Cancer anti-angiogenesis vaccines: is the tumor vasculature antigenically unique? J Transl Med 2015;13:340. [21] Ribatti D, Crivellato E, Vacca A. Inflammation and antiangiogenesis in cancer. Curr Med Chem 2012;19(7):955–60. [22] Yan M, Lesyk G, Radziwon-Balicka A, Jurasz P. Pharmacological regula- tion of platelet factors that influence tumor angiogenesis. Semin Oncol 2014;41(3):370–7. [23] Mousa SA, Lin HY, Tang HY, Hercbergs A, Luidens MK, Davis PJ. Modulation of angiogenesis by thyroid hormone and hormone analogues: implications for cancer management. Angiogenesis 2014;17(3):463–9. [24] Davis PJ, Sudha T, Lin HY, Mousa SA. Thyroid hormone, hormone analogs, and angiogenesis. Compr Physiol 2015;6(1):353–62. CHAPTER 1 Angiogenesis and Anti-Angiogenesis Strategies in Cancer Shaker A. Mousa and Paul J. Davis Contents Process of Angiogenesis 2 Angiogenesis in Cancer 3 Strategies 5 Current Examples of Cancer Treatment Agents that Block Angiogenesis 6 Side Effects of Angiogenesis Inhibitors 7 Angiogenesis and Angiogenesis Inhibitors: Potential Anti-Cancer Therapeutic Efficacy 7 Targeting of VEGF 7 Additional Anti-Angiogenesis Strategies in Cancers 8 Kininostatin 8 Alpha 3 Chain of Type IV Collagen 9 Matrix Metalloproteinases 9 2-Methoxyestradiol 9 Small Molecule Integrin Antagonists 10 Nutraceutical-Derived Polyphenols 10 Anti-Angiogenesis Therapy in Hematologic Cancer: Multiple Myeloma 10 Anti-Coagulants and Angiogenesis 11 Possible Mechanisms of Acquired Resistance to Anti-Angiogenic Drugs 12 Standard Chemotherapy Versus Angiogenesis Inhibitors 13 Anti-Angiogenesis Agents and Thrombosis 13 Diagnostic Imaging of Angiogenesis 13 microRNA and Angiogenesis Modulation 14 References 14 Anti-Angiogenesis Strategies in Cancer Therapies http://dx.doi.org/10.1016/B978-0-12-802576-5.00001-2 1 Copyright © 2017 Elsevier Inc. All rights reserved. 2 Anti-Angiogenesis Strategies in Cancer Therapies PROCESS OF ANGIOGENESIS Angiogenesis is a complex process in which endogenous local or systemic chemical signals coordinate functions of endothelial cells and smooth muscle cells. Both repair of damaged blood vessels and the formation of new blood vessels can be achieved with these signals. Another set of chemical signals, angiogenesis inhibitors (Table 1.1), may systematically disrupt blood vessel formation or support removal of existing vessels, for example, at the conclusion of an inflammatory response. In the setting of homeostasis, the stimulating and inhibiting chemical signals are balanced and blood vessels form only as they are needed. Angiogenic support is critical to growth and spread of cancer. Growth of localized tumors beyond a few millimeters in size Table 1.1 Selected list of endogenous angiogenesis inhibitors and mechanisms of action Endogenous angiogenesis inhibitors Mechanisms Soluble VEGF-1 Decoy receptors for VEGF-B Angiostatin Suppress EC adhesion, migration, proliferation Thrombospondin-1 and -2 Suppress EC adhesion, migration, proliferation Angiopoietin-2 Oppose angiopoietin-1 Platelet factor-4 Inhibit bFGF (FGF2) and VEGF binding Endostatin Suppress EC adhesion, migration, proliferation Anti-thrombin III fragment Suppress EC adhesion, migration, proliferation Osteopontin Serve as ligand for integrin binding Collagen Substrate for MMPs Kininogen domains Suppress EC adhesion, migration, proliferation Tissue factor pathways inhibitor Antagonist for tissue factor Abbreviations: bFGF, basic fibroblast growth factor; EC, endothelial cell; MMP, matrix metal- loproteinase; VEGF, vascular endothelial growth factor. Angiogenesis and Anti-Angiogenesis Strategies in Cancer 3 requires local angiogenesis. Tumor cells generate new blood vessel formation by releasing proangiogenic chemical signals. Normal cells proximal to cancer cells may also support a proangiogenic response via signaling molecules. Local neovascularization supplies growing tumors with oxygen and essential nutrients, supports tumor extension and invasion into nearby normal tissue, and is essential to distant metastasis [1,2]. ANGIOGENESIS IN CANCER As in normal tissues, tumor tissue is unable to grow or metasta- size locally or systemically without angiogenic support. The vessels supply oxygen and nutrients required for growth [2]. The hypoxic tumor cell, for example, at the center of a typically spheroid cancer in situ, will not divide. This state may serve as a survival mechanism when such cells are exposed to therapeutic measures—radiation or certain chemotherapeutic agents—that disrupt DNA only when it is undergoing division. The walls of blood vessels are endothelial cells that divide and migrate in response to local signals. The sequential steps of new blood vessel creation include activation of the endothelial cell wall of an existing small blood vessel (capillary), secretion of metallo- proteinase enzymes that degrade the proteinaceous extracellular matrix (surrounding tissue), invasion of the matrix, and then cell division. String-like lattices of new endothelial cells organize into hollow tubes, resulting in new blood vessel networks that enable surrounding (cancer) tissue growth [2–4]. In nonmalignant tissues, endothelial cells are largely dormant. In growing cancers, endothelial cells are vigorously active. When needed in normal tissues or organs, new capillary growth is closely regulated by release of factors that activate endothelial cells and factors (Table 1.1) that are inhibitory [2,3]. Such a balance is less apparent in cancers, where anti-angiogenic factor production is of course reduced. Among many proteins, known to activate endothelial cell growth and motility, are angiogenin, epidermal growth factor (EGF),