Angiogenesis & Therapeutic Targets In Cancer


by

Malay Chatterjee

DOI: 10.2174/97816080500791100101
eISBN: 978-1-60805-007-9, 2010
ISBN: 978-1-60805-573-9

  
  


Indexed in: Chemical Abstracts, Scopus

Angiogenesis plays rate limiting roles in tumor growth and invasion. Angiogenesis inhibition has been proposed as a general strategy t...[view complete introduction]
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Table of Contents

Foreword , Pp. i

Dominic Fan

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Preface , Pp. ii-iii (2)

Jaak Ph. Janssens

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Acknowledgement , Pp. iv

Malay Chatterjee

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Contributors , Pp. v-viii (4)

Malay Chatterjee, Ajay Rana and Basabi Rana

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Angiogenesis: Antiangiogenesis Strategy and Angiogenesis Inhibitors , Pp. 1-17 (17)

Theodora Kerenidi and Kostas Syrigos

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Angiogenesis and Gastrointestinal Cancer , Pp. 18-30 (13)

Ellen Kossoff and Wen W. Ma

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Breast Cancer Prevention and Treatment with Dietary Agents Affecting Angiogenesis: Progress and Promise , Pp. 31-44 (14)

Anupam Bishayee

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Angiogenesis in Cancer: Therapeutic Targets and Angiogenesis Inhibitors , Pp. 45-67 (23)

Ana R. Quesada and Miguel Angel Medina

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Angiogenesis in Breast Cancer: Molecular Markers, Therapeutic Targets, Antiangiogenic Therapy & Inhibitors , Pp. 68-89 (22)

Carmen Silvia Passos Lima, Gustavo Jacob Lourenco and Jose Augusto Rinck Jr.

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Receptor Tyrosine Kinases in Human Schwannoma , Pp. 90-98 (9)

C Oliver Hanemann and Sylwia Ammoun

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Angiogenesis and Lung Cancer: Antiangiogenic Agents and Therapy , Pp. 99-134 (36)

Mai Har Sham and Kexia Cai

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Angiogenesis and Gastric Cancer: Molecular Pathways & Therapeutic Targets , Pp. 135-146 (12)

C. Moser and O. Stoeltzing

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Angiogenesis and Breast Cancer: Targets and Therapies , Pp. 147-164 (18)

S. Martin and H. Evans

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Translational Studies on the Bone Marrow Microenvironment in Multiple Myeloma: Experimental Models and Emerging Therapeutical Strategies , Pp. 165-179 (15)

Pierfrancesco Tassone, Teresa Calimeri, Marco Rossi, Maria Teresa Di Martino, Paola Neri and Pierosandro Tagliaferri

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Targeted Therapy in Renal Cell Carcinoma , Pp. 180-189 (10)

G. Gasparini and R. Longo

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Surrogate Markers of Antiangiogenic Therapies , Pp. 190-208 (19)

Epie Boven, Martijn R. Meijerink and Laura Vroling

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TGF-β Signaling Dictates Apoptotic and Angiogenic Response During Prostate Cancer Progression , Pp. 209-218 (10)

Natasha Kyprianou and Joanne Collazo

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Index , Pp. 219-225 (7)

Malay Chatterjee, Ajay Rana and Basabi Rana

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Foreword

In 1889, Dr. Stephen Paget investigated the pattern of metastasis in over 700 patients with a variety of cancers. From his studies he concluded that the process of metastasis [1] was not random but rather regulated by a proper interplay between the cancer cells (seed) and the organ microenvironment (soil) of the host. His "seed and soil" hypothesis laid one of the major milestones in the biology of cancer metastasis. That was largely forgotten for over 100 years until Dr. Isaiah J. Fidler awaken Dr. Paget's work and fortified the "seed and soil" hypothesis [2] with three crucial principles: (1) neoplasms are biologically heterogeneous and contain subpopulations of cells with different angiogenic, invasive, and metastatic properties; (2) the process of metastasis is selective for cells that succeed in invasion, embolization, survival in the circulation, arrest in a distant capillary bed, and extravasation into and multiplication within the organ parenchyma; and (3) the outcome of metastasis depends on multiple interactions ("cross-talk") of metastatic cells with homeostatic mechanisms, which the tumor cells can usurp. Dr. Fidler further gave emphasis to the principle that therapy of metastasis can be targeted not only against tumor cells but also against the homeostatic factors that promote tumor cell growth, survival, angiogenesis, invasion, and metastasis. These seminal concepts, together with Dr. Judah Folkman's shaping statement in 1971 that all cancer tumors are angiogenesis-dependent, defined the fields of cancer metastasis and angiogenesis [3]

It is indeed my great pleasure to prologue the making of the monogram "Angiogenesis and Therapeutic Targets in Cancer" organized and edited by Professor Malay Chatterjee. This book encompasses many important areas in the therapy of cancer by targeting various parameters of the angiogenesis process, such as angiogenesis inhibitors, dietary agents that affect angiogenesis, molecular markers for therapy, microenvironment, receptor tyrosine kinases, and signal transduction pathways; of the breast, gastric, lung, prostate, renal cancers as well as Schwannoma and multiple myeloma. I look forward to a stimulating monogram and a successful press.

I hold in true and wish therefore to share in this monogram my personal principle that "for tumor progression and cancer metastasis are not random - treatments and cure is logical and eventual".

Dominic Fan
The University of Texas
M.D. Anderson Cancer Center
Houston, Texas

REFERENCES

[1] Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1:571-573, 1889.

[2] Fidler I. J. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited (Timeline). Nat. Rev. Cancer 3:3453-3458, 2003.

[3] Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285:1182-1186. 1971.


Preface

A variety of cancers are known to originate in epithelial structures and require stromal support to become invasive. This dual mechanism is applicable to nearly all types of cancer. Further growth needs neoangiogenesis, a tumor dependent proliferation of vascular vessels to overcome hypoxia and subsequent growth stop. Metastasis, a common feature of cancer, needs stromal factors and neoangiogenesis as well. Continuous interplay between cancer cells and stroma is a prerequisite for invasion and expansion. Elucidation of neoangiogenic pathways may lead to therapeutic measures; those that convert a progressing cancer into chronic disease, offering a reasonable alternative when cure with classical drugs becomes remote. Other diseases can be approached similarly, including age-related macular degeneration and even therapeutic angiogenesis to treat ischemic disorders.

The concept of targeting neoangiogenesis to inhibit tumor growth has been proposed for a number of years and several approaches to block or disrupt tumor neoangiogenesis have been widely explored. Nowadays it is one of the most intensively studied areas in oncological research. This book will provide a substantial overview of contemporary applications, research and hope. Before going into various types of cancers, like cancers of the lung, kidney, breast, prostate as well as multiple myeloma, gastrointestinal cancer, and Schwannoma, the book will present the latest findings in molecular biology of vessel formation and related processes. The combination of pathways provides opportunities for novel therapies that are extremely welcome in future oncology

When transformed cells escape control, a large number of metabolic steps need to be taken before effective cancerous growth can be expected. Among these is protection against immunological resistance, hypoxia, local inhibiting growth factors etc. Angiogenesis is another dynamic feature of invading cancer. The formation of new blood vessels is a complex, multi-step process, where endothelial cells play a pivotal role.

The role of angiogenesis in renal cell cancer has been tremendously explored because contemporary treatments fail to provide efficient tumor control. Systemic cytokine therapy is rather disappointing but remains nevertheless standard of care, so far. New research points to angiogenesis and novel types of protein kinase pathways that regulate cell growth, proliferation, motility, survival and transcription. Clinical assessment of these local phenomena is a matter of passionate research that needs adequate tools and standardization.

Anti-angiogenic therapy for breast cancer has entered clinical routine in 2008. But many companies are exploring similar approaches and some will be ready in a few years from now. Breast cancer is a rather slow progressing disease once metastasized. As is the case for hormonal treatments, anti-angiogenic therapies can convert the malignancy in a chronic disease. It is no surprise to find lifestyle factors being involved in the angiogenic process providing opportunities to retard the disease. Several foods have direct effects on stromal acceptance and resistance towards cancer invasion and growth. Some of these factors may play a critical role in prevention as well. For therapy, novel targeted molecular therapy and in particular anti-angiogenic agents, are being investigated in numerous clinical trials

Prostate cancer continues to be a challenge for oncologists. Controversy about the initial approach and treatment of hormone resistant cancers lead to attempts to novel targeted therapies. Special emphasis is given to the role of specific tumor-associated antigens and related therapeutic targets. Special attention is going to tumor growth factor beta signaling as treatment target in advanced disease.

Multiple myeloma has become a treatable disease for a number of years now. The bone marrow microenvironment is considered the best target; even from early stages. A wide variety of new compounds target this area. New minimal invasive tools provide opportunities to study surrogate markers that will shorten the investigational period and individualize therapies for tailoring patient's needs.

One of the first applications of anti-angiogenic treatments was colorectal cancer because this entity expresses elevated levels of vascular endothelial growth factor. Recent attention has been given to hepatocellular cancer. Downstream pathways of the vascular endothelial growth factor receptor are in the focus of contemporary research. Gastric cancer remains another therapeutic challenge, in particular for advanced stages. Molecular targeting agents, like those aiming at the angiogenic cascade, show promise.

Lung cancer, the most lethal cancer world-wide, cannot escape research on pro-angiogenic signaling. Although gene therapy with viral vectors continues to be promising, anti-angiogenic factors can provide a valuable addition to cytotoxic and local therapies.

A chapter is devoted to the role of over expressed receptor tyrosine kinase signaling pathway in schwannoma providing an excellent target for disease control

Drug development is a multi-step process that includes basic research, patent validation, extensive and long-lasting clinical trials, registration, reimbursement and commercialization before the patent protection ends. In some instances and countries, commercialization even fails to start before patents close on protection. Drug development is not only extremely expensive but also risky. Hence the need for shortening the developmental process and a way to achieve this is the search for surrogate markers of anti-angiogenic processes and therapy outcome. One of the most obvious options is non-invasive imaging and minimal invasive tools, detection of circulating angiogenic substances and activated endothelial cells to be considered. A critical assessment of these surrogate markers and how they can be retrieved is an essential part of drug development.

A plethora of angiogenesis inhibitors are currently subjected to clinical trials while a few of them have been approved for clinical use. The drugs can be divided into several categories, including growth factor inhibitors, endothelial cell signal transduction inhibitors, inhibitors of endothelial cell proliferation, inhibitors of matrix metalloproteinases, and inhibitors of endothelial cell survival. For practical purposes, two groups can be remembered: those that inhibit a number of growth factors and those that inhibit breakdown of the basement membrane and extracellular matrix. Unlike tumor cells, tumor associated endothelial cells seem not to develop resistance to anti-angiogenic agents. Furthermore, anti-angiogenic agents are generally cytostatic rather than cytotoxic. Finally, they are considered well-tolerated.

Because antiangiogenic therapy is unlikely to induce tumor regression, the criteria for efficacy must be evaluated by means other than the standard response criteria used to evaluate cytotoxic chemotherapy. Further, the redundancy of molecules responsible for the angiogenic process suggests that it is unlikely that a single antiangiogenic agent will provide prolonged inhibition of angiogenesis. Nevertheless, the understanding of the basic principles that drive tumor angiogenesis will lead to the development of therapies that will likely prolong survival without the toxicity associated with standard chemotherapy.

Jaak Ph. Janssens MD, PhD
Oncologist
Editor-in-Chief of European Journal of Cancer Prevention
&
President of European Cancer Prevention Organisation
University of Limburg
Belgium,UK

List of Contributors

Editor(s):
Malay Chatterjee
Jadavpur University
India




Co-Editor(s):
Ajay Rana
Loyola University Medical Center
USA


Basabi Rana
Loyola University Medical Center
USA




Contributor(s):
Theodora Kerenidi
Respiratory Department
Thessaly School of Medicine
Magniton 32
Volos, 38333
Greece


Kostas Syrigos
Oncology Unit GPP, Athens School of Medicine
Greece


Wen W. Ma
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo
NY , 14263
USA


Ellen Kossoff
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo
NY , 14263
USA


Anupam Bishayee
Department of Pharmaceutical Sciences
Northeastern Ohio Universities Colleges of Medicine and Pharmacy
4209 State Route 44
Rootstown
OH, 44272
USA


Ana R. Quesada
Department of Molecular Biology and Biochemistry Faculty of Science
University of Málaga
and CIBER de Enfermedades Raras (CIBERER)
Málaga , 29071
Spain


Miguel Ángel Medina
Department of Molecular Biology and Biochemistry Faculty of Science
University of Málaga
and CIBER de Enfermedades Raras (CIBERER)
Málaga , 29071
Spain


Carmen Silvia Passos Lima
Clinical Oncology Service Department of Internal Medicine
Faculty of Medical Sciences, State University of Campinas
Campinas
SP
Brazil


Gustavo Jacob Lourenço
Department of Internal Medicine Faculty of Medical Sciences
State University of Campinas
Campinas
SP
Brazil


José Augusto Rinck
Department of Internal Medicine Faculty of Medical Sciences
State University of Campinas
Campinas
SP
Brazil


C. Oliver Hanemann
Clinical Neurobiology
Peninsula College of Medicine and Dentistry
The John Bull Building Tamar Science Park Research Way
Plymouth
PL6 8BU
UK


Sylwia Ammoun
Clinical Neurobiology
Peninsula College of Medicine and Dentistry
The John Bull Building Tamar Science Park Research Way
Plymouth
PL6 8BU
UK


Dr. Mai Har Sham
Department of Biochemistry,
Li Ka Shing Faculty of Medicine, The University of Hong Kong
21 Sassoon Road, Pokfulam
Hong Kong
SAR
China


Kexia Cai
Department of Biochemistry
Li Ka Shing Faculty of Medicine, The University of Hong Kong
21 Sassoon Road Pokfulam
Hong Kong
SAR
China


Oliver Stoeltzing
Departments of Hepatobiliary Surgery and Transplantation Surgery
University Medical Center Hamburg-Eppendorf Martinistr
Hamburg 52, 20246
Germany


C. Moser
Departments of Surgery and Surgical Oncology
University of Regensburg Medical Center
Regensburg, 93042
Germany


Pierfrancesco Tassone
Medical Oncology Unit and Center for Innovative Treatments in Medical Oncology
University “Magna Græcia” and Tommaso Campanella Cancer Center Viale Europa
Catanzaro, I-88100
Italy


Teresa Calimeri
Medical Oncology Unit and Center for Innovative Treatments in Medical Oncology
University “Magna Græcia” and Tommaso Campanella Cancer Center Viale Europa
Catanzaro , I-88100
Italy


Marco Rossi
Medical Oncology Unit and Center for Innovative Treatments in Medical Oncology
University “Magna Græcia” and Tommaso Campanella Cancer Center Viale Europa
Catanzaro, I-88100
Italy


Maria Teresa Di Martino
Medical Oncology Unit and Center for Innovative Treatments in Medical Oncology
University “Magna Græcia”and Tommaso Campanella Cancer Center Viale Europa
Catanzaro
I, 88100
Italy


Paola Neri
Medical Oncology Unit and Center for Innovative Treatments in Medical Oncology
University “Magna Græcia”and Tommaso Campanella Cancer Center Viale Europa
Catanzaro
AB, I-88100
Italy


G. Gasparini
Division of Medical Oncology ‘San Filippo Neri’ Hospital
Via Martinotti 20
Rome, 00135
Italy


R. Longo
Division of Medical Oncology ‘San Filippo Neri’ Hospital
Via Martinotti 20
Rome, 00135
Italy


Epie Boven
VU University medical center Department of Medical Oncology
De Boelelaan 1117
Amsterdam
HV , 1081
The Netherlands


Martijn R. Meijerink
VU University medical center Department of Radiology
De Boelelaan 1117
Amsterdam
HV , 1081
The Netherlands


Laura Vroling
VU University medical center Department of Medical Oncology
De Boelelaan 1117
Amsterdam
HV , 1081
The Netherlands


Astrid A.M. van der Veldt
VU University medical center Department of Medical Oncology
De Boelelaan 1117
Amsterdam
HV , 1081
The Netherlands


Natasha Kyprianou
Division of Urology
Combs Cancer Building Room, 306, University of Kentucky Medical Center
800, Rose Street
Lexington
KY , 40536



Joanne Collazo
Departments of Toxicology Urology/Surgery and Department of Molecular and Cellular Biochemistry College of Medicine
University of Kentucky College of Medicine and Markey Cancer Center
Combs Blg. Room 306 800 Rose Street
Lexington
KY, 40536
U.S.A


Stewart Martin
School of Molecular Medical Sciences
Division of Clinical Oncology University of Nottingham
Nottingham University Hospitals City Hospital Campus
Nottingham
NG5 1PB
UK


H. Evans
School of Molecular Medical Sciences
Division of Clinical Oncology University of Nottingham
Nottingham University Hospitals City Hospital Campus
Nottingham
NG5 1PB
UK




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