The first part of the book gives an introduction into the cell and molecular biology of cancer, focusing on the key mechanisms of cancer formation, The second part of the book introduces the main signaling transduction mechanisms responsible for carcinogenesis and compares their function in healthy versus cancer cells, In contrast to the complexity of its topic, the text is easy to read, 32 specially prepared teaching videos on key concepts and pathways in cancer signaling are available online for users of the print edition and have been integrated into the text in the enhanced e-book edition,
Christoph Wagener is Professor of Clinical Biochemistry and former director of the Institute of Clinical Chemistry at the University Medical Center Hamburg-Eppendorf, Germany, His areas of research are the interaction of tumor cells with their microenvironment, and molecular approaches to tumor diagnosis, Professor Wagener has authored more than 100 original scientific publications, 15 scientific reviews and 13 book chapters, Together with Oliver Muller, he published the text book 'Molekulare Onkologie' and the 'Onkoview Videos', which can be viewed on YouTube, Book and videos have received excellent reviews from readers and viewers,
Carol Stocking is Head of the Research Group Retroviral Pathogenesis at the Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology in Hamburg, Germany, She is a highly regarded expert in the field of leukemogenesis and hematology, Her areas of research are gene regulation, molecular control of differentiation, and hematopoietic stem cells, Dr, Stocking has authored more than 120 original publications in top international journals and 20 book chapters,
Oliver Muller is Professor for Applied Life Sciences at the University for Applied Sciences Kaiserslautern, Germany, He holds academic degrees in both biochemistry and medicine, His areas of research are the intracellular signal transduction and the genes and proteins involved in carcinogenesis, Professor Muller is author of more than 80 original articles, 11 patents, 15 scientific reviews and 4 book chapters, His work was honoured by several science awards,
Dieses verständlich geschriebene Lehrbuch vermittelt alles Wissenswerte rund um die molekulare Onkologie. Vor allem die bei vielen Krebsarten wichtigen Signalwege werden detailliert dargestellt. Eine Vielzahl von Lehrvideos machen das Thema erfahrbar.
Autorentext
Christoph Wagener is Professor of Clinical Biochemistry and former director of the Institute of Clinical Chemistry at the University Medical Center Hamburg-Eppendorf, Germany. His areas of research are the interaction of tumor cells with their microenvironment, and molecular approaches to tumor diagnosis. Professor Wagener has authored more than 100 original scientific publications, 15 scientific reviews and 13 book chapters. Together with Oliver Muller, he published the text book 'Molekulare Onkologie' and the 'Onkoview Videos', which can be viewed on YouTube. Book and videos have received excellent reviews from readers and viewers.
Carol Stocking is Head of the Research Group Retroviral Pathogenesis at the Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology in Hamburg, Germany. She is a highly regarded expert in the field of leukemogenesis and hematology. Her areas of research are gene regulation, molecular control of differentiation, and hematopoietic stem cells. Dr. Stocking has authored more than 120 original publications in top international journals and 20 book chapters.
Oliver Muller is Professor for Applied Life Sciences at the University for Applied Sciences Kaiserslautern, Germany. He holds academic degrees in both biochemistry and medicine. His areas of research are the intracellular signal transduction and the genes and proteins involved in carcinogenesis. Professor Muller is author of more than 80 original articles, 11 patents, 15 scientific reviews and 4 book chapters. His work was honoured by several science awards.
Inhalt
Preface XV
Acknowledgments XXI
List of Abbreviations XXIII
About the Companion Website XXIX
1 General Aspects of Signal Transduction and Cancer Therapy 1
1.1 General Principles of Signal Transduction 2
1.1.1 Biological Signals have to be Processed 2
1.1.2 What is a Signal Transduction Pathway? 2
1.1.3 Mechanisms of Direct Signal Transduction 4
1.1.4 The Interactome Gives Insight into the Signaling Network 5
1.1.5 Protein Domains for ProteinProtein Interaction and Signal Transduction 6
1.1.6 Functions of Mutated Proteins in Tumor Cells 8
1.2 Drugs against Cancer 10
1.2.1 Terms and Definitions 10
1.2.2 The Steps from a Normal Cell to a Tumor 10
1.2.3 Interference Levels ofTherapeutic Drugs 11
1.2.4 Drugs Attacking the Whole Cell 12
1.2.4.1 DNA Alkylating Drugs 13
1.2.5 Process-Blocking Drugs 14
1.2.5.1 Drugs Blocking Synthesis of DNA and RNA 14
1.2.5.2 Drugs Blocking the Synthesis of DNA and RNA Precursor Molecules 15
1.2.5.3 Drugs Blocking Dynamics of Microtubules 16
1.2.6 Innovative Molecule-Interfering Drugs 18
1.2.7 Fast-Dividing Normal Cells and Slowly Dividing Tumor Cells: Side Effects and Relapse 19
1.2.8 Drug Resistance 19
1.2.8.1 Drugs Circumventing Resistance 19
1.3 Outlook 20
2 Tumor Cell Heterogeneity and Resistance to Targeted Therapy 23
2.1 The Genetic Basis of Tumorigenesis 24
2.2 Clonal Heterogeneity 24
2.2.1 Clonal Origin of Tumors 24
2.2.2 Clonal Evolution 26
2.2.3 The Time Course of Clonal Evolution 30
2.2.4 Clonal Evolution and Resistance toTherapy 32
2.2.5 Targeting Essential Drivers (Driver Addiction) 34
2.2.6 Resistance by Alternative Pathway Activation 36
2.2.7 Overcoming Resistance by Combinatorial Therapies 36
2.3 Tumor Stem Cells and Tumor Cell Hierarchies 37
2.4 Epigenetics and Phenotypic Plasticity 40
2.5 Microenvironment 42
2.6 Outlook 43
3 Cell Cycle of Tumor Cells 47
3.1 Properties of Tumor Cells 48
3.1.1 Differences between Tumor Cells and Normal Cells In vitro 49
3.1.2 Regulation of Cell Number 49
3.2 The Cell Cycle 50
3.2.1 Checkpoints 51
3.2.2 Cyclins 52
3.2.3 Cyclin-Dependent Kinases (CDKs) 53
3.2.4 The Retinoblastoma-Associated Protein Rb as Regulator of the Cell Cycle 54
3.2.5 Inhibitors of CDKs 54
3.2.6 Checkpoints and DNA Integrity 55
3.2.7 The Repair Mechanism Depends on the Cell Cycle Phase 57
3.2.8 Tumor-Relevant Proteins in the Cell Cycle 57
3.3 The Cell Cycle as Therapeutic Target 58
3.3.1 Small Compounds Inhibiting Cell-Cycle-Dependent Kinases as Anticancer Drugs 59
3.4 Outlook 60
4 Cell Aging and Cell Death 63
4.1 A Cell's Journey through Life 64
4.2 Cellular Aging and Senescence 64
4.2.1 Replicative Senescence 65
4.2.2 Shortening of Chromosomal Telomeres during Replication 67
4.2.3 Chromosomal Telomeres 67
4.2.4 Telomerase 69
4.2.5 Animal Models 72
4.2…