Recent Results in Cancer Research

Transcription

1 Recent Results 176 in Cancer Research Managing Editors P. M. Schlag, Berlin H.-J. Senn, St. Gallen Associate Editors P. Kleihues, Zürich F. Stiefel, Lausanne B. Groner, Frankfurt A. Wallgren, Göteborg Founding Editor P. Rentchnik, Geneva

2 M. Dietel (Ed.) Targeted Therapies in Cancer With 57 Figures and 25 Tables 123

3 Prof. Dr. med. Manfred Dietel Institut für Pathologie Humboldt-Universität zu Berlin Schumanstr Library of Congress Control Number: ISSN ISBN Springer Berlin Heidelberg New York This work is subject to copyright. All rights reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in databanks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September, 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer is a part of Springer Science + Business Media springer.com Springer-Verlag Berlin Heidelberg 2007 The use of general descriptive names, registered names, trademarks, 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. Product liability: The publisher cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Editor: Dr. Ute Heilmann, Heidelberg Desk editor: Dörthe Mennecke-Bühler, Heidelberg Production editor: Nadja Kroke, Leipzig Cover design: Frido Steinen-Broo, estudio Calamar, Spain Typesetting: LE-TEX Jelonek, Schmidt & Vöckler GbR, Leipzig Printed on acid-free paper SPIN /3100/YL

4 Preface V Over the past 50 years, the efficacy of cancer chemotherapy has improved considerably. Nonetheless, particularly in the metastatic situation, clinical outcome parameters, such as overall survival, have changed only modestly. This fact continues to represent a tremendous obligation for the scientific community and the pharmaceutical industry to develop new approaches in the fight against cancer. The enormous progress in the knowledge of functional tumor cell biology, in particular of the molecular pathways and regulatory processes within tumor cells, has given researchers the chance to identify more key molecules as targets for specific drugs. These could exploit alreadyproven therapeutic strategies, such as humanized antibodies or small-molecule inhibitors directed against growth regulatory kinases, or completely novel approaches. The current volume aims at providing an up-todate report on the field of targeted cancer therapy. Contributions encompass basic and translational research as well as clinical experience and they outline functional mechanisms, diagnostic algorithms, predictive approaches, patient-related studies, and up-coming challenges in this stimulating but also controversial field of anticancer research. Manfred Dietel Peter Schlag

5 Contents Contents VII Part I Prediction of Tumor Behavior 1 Beyond Typing and Grading: Target Analysis in Individualized Therapy as a New Challenge for Tumour Pathology... 3 Hans H. Kreipe, Reinhard von Wasielewski 2 Oncogenic Signaling Pathways and Deregulated Target Genes... 7 Reinhold Schäfer, Anja Schramme, Oleg I. Tchernitsa, Christine Sers 3 Predictive Pathology of Cytostatic Drug Resistance and New Anti-cancer Targets Manfred Dietel 4 Prediction of Response to Neoadjuvant Chemotherapy in Carcinomas of the Upper Gastrointestinal Tract Heinz Höfler, Rupert Langer, Katja Ott, Gisela Keller 5 Resistance-Associated Signatures in Breast Cancer Balázs Györffy 6 Resistance to Chemotherapy in Ovarian Carcinoma Hermann Lage, Carsten Denkert 7 Clinical, Biological, and Molecular Aspects of Metastasis in Colorectal Cancer Ulrike Stein, Peter M. Schlag 8 Prediction of Efficacy and Side Effects of Chemotherapy in Colorectal Cancer Jan Stoehlmacher

6 VIII Contents 9 Proteomic Expression Profiling of Breast Cancer Hans Neubauer, Tanja Fehm, Christina Schütz, Runa Speer, Erich Solomayer, André Schrattenholz, Michael A. Cahill, Raffael Kurek Part II Targeted Therapy and Clinical Applications 10 Targeted Therapy and Blood Brain Barrier Agnieszka Korfel, Eckhard Thiel 11 Cetuximab: Appraisal of a Novel Drug Against Colorectal Cancer Bert Hildebrandt, Philipp le Coutre, Annett Nicolaou, Konrad Kölble, Hanno Riess, Bernd Dörken 12 C-kit, GIST, and Imatinib Jan Siehl, Eckhard Thiel 13 Antibody Therapy in Non-Hodgkin s Lymphoma: The Role of Rituximab, 90Y-Ibritumomab Tiuxetan, and Alemtuzumab Thomas Fietz, Eckhard Thiel 14 Molecular and Clinical Aspects of Proteasome Inhibition in the Treatment of Cancer Ivana Zavrski, Christian Jakob, Martin Kaiser, Claudia Fleissner, Ulrike Heider, Orhan Sezer 15 Individualized Target Therapy of Malignant Lymphomas: An Outlook Ioannis Anagnostopoulos 16 Antiangiogenesis, Anti-VEGF(R) and Outlook Iver Petersen 17 Morphological Detection of Hormone and Growth Factor Receptors in Breast Cancer Konrad Kölble

7 Contents IX Part III Prospects for Development 18 Antigen-Specific Cancer Vaccines Ulrich Keilholz 19 Therapeutic Vaccination for the Treatment of Malignant Melanoma Peter Walden 20 Monoclonal and Recombinant Antibodies with T Cell Receptor-Like Reactivity Andreas Ziegler, Pierre G. Coulie, Barbara Uchańska-Ziegler 21 New Molecular Therapy Targets in Acute Myeloid Leukemia Utz Krug, Hubert Serve, Carsten Müller-Tidow, Rolf M. Mesters, Björn Steffen, Thomas Büchner, Wolfgang E. Berdel

8 List of Contributors XI List of Contributors Ioannis Anagnostopoulos, MD Institut für Pathologie Campus Benjamin Franklin Wolfgang E. Berdel, MD Thomas Büchner, MD Michael A. Cahill, PhD ProteoSys AG Carl-Zeiss-Str Mainz Pierre G. Coulie, MD, PhD Christian de Duve Institute of Cellular Pathology Université catholique de Louvain 1200 Brussels Belgium Philipp le Coutre, MD, PhD Centrum für Tumormedizin Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie Carsten Denkert, MD Campus Mitte Manfred Dietel, Prof. Dr. med. Dr. hc. Humboldt University Bernd Dörken, MD, PhD Centrum für Tumormedizin Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie Tanja Fehm, MD University Women s Hospital Thomas Fietz, MD Hematology, Oncology and Transfusion Medicine Campus Benjamin Franklin Claudia Fleissner, MD

9 XII Balázs Györffy, MD, PhD Joint Research Laboratory Semmelweis University Budapest and Hungarian Academy of Sciences Bókay u. 53/ Budapest Hungary Ulrike Heider, MD Bert Hildebrandt, MD Centrum für Tumormedizin Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie Heinz Höfler, MD Technical University Munich Trogerstr Munich Christian Jakob, MD Martin Kaiser, MD Ulrich Keilholz, MD Professor of Medicine Department of Medicine III Campus Benjamin Franklin Gisela Keller, PhD Technical University Munich Trogerstr Munich List of Contributors Konrad Kölble, MD, PhD Centrum 5 für diagnostische und präventive Labormedizin Institut für Pathologie Campus Mitte Agnieszka Korfel, MD Medizinische Klinik III Hämatologie, Onkologie und Transfusionsmedizin Hans H. Kreipe, MD Institut für Pathologie der Medizinischen Hochschule Hannover Utz Krug, MD Raffael Kurek, MD University Women s Hospital Hermann Lage, PhD MD Campus Mitte

10 List of Contributors XIII Rupert Langer, MD Technical University Munich Trogerstr Munich Rolf M. Mesters, MD Carsten Müller-Tidow, MD Hans Neubauer, PhD Universitäts-Frauenklinik Tübingen Calwerstr. 7/6 Annett Nicolaou, MD Centrum für Tumormedizin Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie Katja Ott, MD Department of Surgery Technical University Munich Trogerstr Munich Iver Petersen, MD Institut für Pathologie Rudolf-Virchow-Haus Humboldt-Universität Berlin Campus Mitte Hanno Riess, MD, PhD Centrum für Tumormedizin Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie Reinhold Schäfer, PhD Laboratory of Molecular Tumor Pathology Peter M. Schlag, MD Robert Rössle Clinic Campus Buch Lindenberger Weg Berlin André Schrattenholz, PhD ProteoSys AG Carl-Zeiss-Str Mainz Anja Schramme, PhD Laboratory of Molecular Tumor Pathology Christina Schütz, PhD University Women s Hospital Christine Sers, PhD Laboratory of Molecular Tumor Pathology

11 XIV Hubert Serve, MD Orhan Sezer, MD Jan Siehl, MD Medizinische Klinik III (Hematology, Oncology and Transfusion Medicine) Campus Benjamin Franklin Erich Solomayer, MD University Women s Hospital Runa Speer, MD University Women s Hospital Björn Steffen, MD Ulrike Stein, PhD Max Delbrück Center for Molecular Medicine Robert-Rössle-Str Berlin Jan Stoehlmacher, MD Department of Internal Medicine I Haematology and Medical Oncology University Hospital Carl Gustav Carus Dresden Fetscherstr Dresden List of Contributors Oleg I. Tchernitsa, MD, PhD Laboratory of Molecular Tumor Pathology Eckhard Thiel, MD PhD Medizinische Klinik III Hematology, Oncology and Transfusion Medicine Campus Benjamin Franklin Barbara Uchańska-Ziegler, PhD Institut für Immungenetik Berlin Peter Walden, ScD Department of Dermatology, Venerology and Allergy Clinical Research Group Tumor Immunology Reinhard von Wasielewski, MD Institut für Pathologie der Medizinischen Hochschule Hannover Ivana Zavrski, MD Andreas Ziegler, PhD Institut für Immungenetik Humboldt-Universität zu Berlin