Progressive Neuroblastoma

Description

Neuroblastoma is a tumor derived from the sympathetic nervous system. It is the most common extracranial solid tumor occurring in children and exhibits a marked variability in outcome when the disease is categorized by clinical (e.g. age or stage) and biologic characteristics. This book gives an introduction into the clinical features of progressive neuroblastoma and focuses on molecular-targeted therapies and immunotherapies of this disease. It has become increasingly clear that MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog) holds a key position in neuroblastic transformation and gene expression in normal and transformed cells. In the 14 chapters important topics such as genomic alterations in neuroblastoma and strategies for indirect molecular targeting of MYCN are discussed. Two chapters, for example, review apoptotic pathways and proapoptotic molecular targets in neuroblastoma, one focusing on the p53 pathway and the extrinsic and intrinsic pathways of apoptosis. Other chapters cover topics related to immunology in neuroblastoma, such as immune regulation in neuroblastoma, immunotherapy related to passive and active vaccination approaches and additional immunotherapy in the treatment of progressive disease. This volume will be essential reading for all clinicians and basic researchers who are involved in delivering health care to patients with progressive neuroblastoma.

Informations

• Publié par: S. Karger AG
• Date de parution: 28 septembre 2015
• Nombre de lectures: 0
• EAN13: 9783318054972
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Progressive Neuroblastoma
Pediatric and Adolescent Medicine
Vol. 20
Series Editor
Wieland Kiess Leipzig
Progressive Neuroblastoma
Innovation and Novel Therapeutic Strategies
Volume Editors
Holger Christiansen Leipzig
Nina Merete Christiansen Leipzig
16 figures, 5 in color, and 6 tables, 2015
Pediatric and Adolescent Medicine Founded 1991 by D. Branski, Jerusalem
_______________________ Prof. Holger Christiansen Department of Pediatric Oncology, Hematology and Hemostaseology University of Leipzig, Leipzig, Germany
_______________________ Dr. Nina Merete Christiansen Department of Pediatric Oncology, Hematology and Hemostaseology University of Leipzig, Leipzig, Germany
Library of Congress Cataloging-in-Publication Data
Progressive neuroblastoma: innovation and novel therapeutic strategies / volume editors, Holger Christiansen, Nina Merete Christiansen.
p. ; cm. -- (Pediatric and adolescent medicine, ISSN 1017-5989 ; vol. 20)
Includes bibliographical references and index.
ISBN 978-3-318-05496-5 (hard cover : alk. paper) -- ISBN 978-3-318-05497-2 (electronic version)
I. Christiansen, Holger, 1957- , editor. II. Christiansen, Nina Merete, editor. III. Series: Pediatric and adolescent medicine ; v. 20. 1017-5989
[DNLM: 1. Neuroblastoma--therapy. 2. Drug Therapy--methods. 3. Immunotherapy--methods. 4. Oncogene Proteins--genetics. 5. Pediatrics--methods. W1 PE163HL v.20 2015 / QZ 380]
RC280.N4
618.92’994806--dc23
2015024044
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents ® and Index Medicus.
Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
© Copyright 2015 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland)
www.karger.com
Printed in Germany on acid-free and non-aging paper (ISO 9706) by Kraft Druck GmbH, Ettlingen
ISSN 1017-5989
e-ISSN 1662-3886
ISBN 978-3-318-05496-5
e-ISBN 978-3-318-05497-2
Contents
Preface
Christiansen, H.; Christiansen, N.M. (Leipzig)
Clinical Introduction
Clinical Features of Progressive Neuroblastoma
Simon, T. (Cologne)
Genomic Alterations
DNA Copy Number Changes and Beyond
Fieuw, A. (Ghent); Schulte, J.H. (Berlin/Heidelberg); De Preter, K.; Speleman, F. (Ghent)
Genomic Alterations and Abnormal Cell Cycle in High-Risk Neuroblastoma
Capasso, M. (Naples); Sidarovich, V.; Quattrone, A. (Trento); Tonini, G.P. (Padua)
Targeting MYCN
MYCN and MicroRNAs
Althoff, K. (Essen); Schulte, J.H. (Berlin/Heidelberg)
MYCN and Its Posttranslational Regulation in Neuroblastoma
Otto, T. (Boston, Mass.)
Apoptosis and Angioneogenesis
Neuroblastoma and the p53 Pathway
Chen, L.; Tweddle, D.A. (Newcastle)
Targeting Cell Death Pathways in Neuroblastoma
Fulda, S. (Frankfurt)
Neuroblastoma and Angiogenesis
Rössler, J. (Freiburg)
Molecular-Targeted Therapy Studies
The Role of the Anaplastic Lymphoma Kinase Receptor in Neuroblastoma
Yeung, C.M.; George, R.E. (Boston, Mass.)
Molecular-Targeted Therapy in Refractory or Relapsed Neuroblastoma
Corbacioglu, S. (Regensburg)
Immunology
Immune Regulation in Neuroblastoma
Fest, S. (Magdeburg); Starke, S. (Leipzig)
Approaches to Passive and Active Vaccination against Neuroblastoma
Lode, H.N. (Greifswald)
Role of Cell Therapy in Neuroblastoma
Bremm, M.; Brehm, C.; Huenecke, S.; Rettinger, E.; Bader, P. (Frankfurt/Main)
Minimal Residual Disease
Minimal Residual Disease in Neuroblastoma
Weber, A. (Giessen)
Author Index
Subject Index
Preface
Neuroblastoma is a tumor derived from the sympathetic nervous system. It is the most common extracranial solid tumor occurring in children, exhibiting marked variability in outcome when the disease is categorized by clinical (e.g. age and stage) and biologic characteristics. This book is focused on immuno- and molecular-targeted therapies in progressive neuroblastoma; an introduction into the clinical features of this disease is given by Simon.
It has become more and more evident from basic research over the last three decades that the oncogene MYCN as a transcriptional activator and repressor of a plethora of cellular pathways in transformed cells is the master regulator in neuroblastic transformation, as well as in neuroblastoma cell regression and progression. At present, we do not understand the principles and forces initiating MYCN transformational activity, but there is an ever-growing body of knowledge of how MYCN regulates gene expression in normal and transformed cells.
Two chapters focus on genomic alterations in neuroblastoma: Fieuw et al. review the identification of MYCN targets in focal DNA copy number changes, and Capasso et al. describe genomic alterations and abnormal cell cycle control.
Althoff and Schulte review the impact of MYCN on miRNA regulation, and how MYCN itself is controlled by miRNAs or by posttranscriptional regulation is reviewed by Otto. In both chapters, strategies for indirect molecular targeting of MYCN are discussed.
Evasion from apoptosis and activation of angiogenesis are important hallmarks of cancer cells and are also known to be regulated by MYCN. Two chapters review apoptotic pathways and proapoptotic molecular targets in neuroblastoma: Chen and Tweddle give an update on the p53 pathway, and Fulda discusses the extrinsic and intrinsic pathways of apoptosis. How angiogenesis in particular can be influenced is described by Rössler.
There are ongoing clinical trials utilizing either an individualized molecular-targeted approach as reviewed by Yeung and George, or an approach taking into account common pathways and mechanisms of resistance as outlined by Corbacioglu.
This volume contains three chapters on immunology in neuroblastoma. Fest and Starke review immune regulation in neuroblastoma. Immunotherapy related to passive and active vaccination approaches is described by Lode. Bremm et al. report on the feasibility and efficacy of haploidentical hematopoietic stem cell transplantation and additional immunotherapy in the treatment of progressive disease.
Monitoring of minimal residual disease is important in a variety of malignancies and might also contribute to improve the outcome of progressive neuroblastoma. Insight into minimal residual disease detection in neuroblastoma is given by Weber.
The editors would like to express their gratitude and appreciation to the authors who are all experts in their field, and they are grateful to the publishers for their help and encouragement during the preparation and assembly of this book.
Holger Christiansen, Leipzig Nina M. Christiansen, Leipzig
Clinical Introduction
Christiansen H, Christiansen NM (eds): Progressive Neuroblastoma: Innovation and Novel Therapeutic Strategies. Pediatr Adolesc Med. Basel, Karger, 2015, vol 20, pp 1-9 (DOI: 10.1159/000382027)
______________________
Clinical Features of Progressive Neuroblastoma
Thorsten Simon
Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany
______________________
Abstract
Progressive neuroblastoma has a high risk of disease recurrence despite cancer treatment. Most patients can be identified at the time of diagnosis either by age over 18 months and the presence of distant metastases, or by amplification of the oncogene MYCN . As the body of knowledge concerning molecular mechanisms of cancer development and progression grows, molecular markers will increasingly substitute clinical factors for precise classification of patients with a high risk of disease progression. Successful treatment of high-risk neuroblastoma patients remains a challenge. State-of-the-art multimodality treatment of high-risk neuroblastoma patients includes intensive induction chemotherapy followed by high-dose chemotherapy with autologous stem cell transplantation, external beam radiation therapy, metaiodobenzylguanidine therapy, surgery and postconsolidation therapy such as isotretinoin or immunotherapy. The value of high-dose metaiodobenzylguanidine therapy and extensive surgery have not yet been proven by prospective trials. Although