Introduction to cancer biology : a concise journey from epidemiology through cell and molecular biology to treatment and prospects

366 Pages·2012·9.992 MB·English

by  Robin Hesketh

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Introduction to Cancer Biology
A Concise Journey from Epidemiology through Cell and Molecular Biology
to Treatment and Prospects
This concise overview of the fundamental concepts of cancer biology is ideal for
students with little or no background in the field. A digestible summary of global
cancer patterns introduces students to the general principles of how cancers arise.
Specific key examples are then used to illustrate the role of mutations in perturbing
signalling pathways in cells, highlighting general principles without overwhelming
students with detail.Later chapters build on this foundation toprovide acomprehen-
sive summary of the major signalling pathwaysthat affect tumourdevelopment.
Reviews of current therapeutic strategies and the impact of whole genome sequen-
cing bring students up to date with important recent developments in the field.
Appendix E summarises the ten major cancers, providing a valuable reference
resource, and further reading sections point students towards helpful review articles,
offering aneasy transition into the scientific literature.
Robin Hesketh hasbeenamemberoftheBiochemistryDepartmentattheUniversity
of Cambridge for over 25 years. He has given lecture courses at all undergraduate
levelsfromfirst-yearmedicinetofourth-yearbiochemistryonawiderangeofcelland
molecular biology topics with a particular focus on cancer. He has also run under-
graduate practicalson a variety of themes and for many years gave tutorials in all of
the Tripos courses taught by the Biochemistry Department. His major research area is
the developmentof anti-angiogenic strategies forthe treatment of cancer.
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Introduction to
Cancer Biology
A Concise Journey from Epidemiology
through Cell and Molecular Biology to
Treatment and Prospects
Robin Hesketh
UniversityofCambridge
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Introductiontocancerbiology/RobinHesketh.
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Includesbibliographicalreferencesandindex.
ISBN978-1-107-01398-8(Hardback)–ISBN978-1-107-60148-2(Paperback)
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CONTENTS
Acknowledgements page ix
Introduction xi
Genenomenclature xv
1 Lessons from epidemiology 1
Incidence 1
Deaths 2
Patterns around the world:how many cancers and what sort? 3
Trends 11
Age 11
Where do we standand isthereany goodnews? 13
Conclusions 17
Key points 17
Key questionsand objectives 19
Further reading: reviews 19
2 Causes of cancer 20
Introduction 20
Infection 21
Radiation 21
Ionising radiation 22
Radon 26
Ultravioletradiation 28
Low-frequency magnetic fields 29
High-frequency magnetic fields (mobile phones) 30
Tobacco 31
Alcohol 33
Tea and coffee 35
Diet:epidemiological studies 35
Obesity 39
Stress 40
Conclusions 40
Key points 41
Key questionsand objectives 42
Further reading: reviews 43
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vi Contents
3 Signalling in normal cells 44
Introduction 44
Enzyme-coupled receptors 45
Receptor tyrosine kinases(RTKs) 47
Intracellular signalling fromactivated tyrosine kinase receptors 49
Activating RAS and MAPK 51
Sustained versustransientactivation of RAS and MAPK 53
Mitogenic activation of cellcycle progression 54
MYC isacentralregulatorof cell growth and proliferation 54
MYC and proliferation 57
Cytokine receptors 58
G-protein-coupled receptors 59
Ligand-gated ion channelreceptors 60
Steroid hormones 60
Conclusions 64
Key points 64
Key questionsand objectives 64
Further reading: reviews 65
4 ‘Cancer genes’: mutations and cancer development 66
Collecting mutations 66
Genetic roulette 67
The cancer genomic landscape 68
Mutations in‘cancer genes’: oncogenes and tumoursuppressor genes 69
Oncogenes 70
The first humanoncogene 71
Whatturns aproto-oncogene into anoncogene? 72
Tumour suppressor genes 85
Whatdoesthe retinoblastoma protein do? 87
Tumour protein53 (TP53 akap53) 88
p53,cellcycle arrest,apoptosis and MYC 89
p53 and cancer 90
P53 isnot entirely atumoursuppressor 91
DNA repair 92
Hereditary cancers 93
Hereditary breastcancer 93
Hereditary colon cancer 94
DNA repeats itself 95
Polymorphisms and cancer 96
Modulatinggene expression withoutmutation: epigenetic changes 96
MicroRNAs (miRNAs) 97
Conclusions 99
Key points 99
Key questionsand objectives 100
Further reading: reviews 100
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vii Contents
5 What is a tumour? 102
Introduction 102
Benign tumours 103
The benign–malignant boundary 106
Types of malignant (non-benign) cancer 107
Whatmakesa cancer cell acancer cell? 107
Cancer cell characteristics 108
Cellgrowth islargely independent of normalsignals 109
Resistance toinhibitory growth signals 110
Resistance tocelldeath 111
Unlimited replicative capacity 115
Induction of angiogenesis 117
Abnormal metabolism 121
Inflammation and the immunesystem 131
The uniqueness of malignancy 136
Metastasis and metastatic potential 136
How does cancer kill you? 146
Conclusions 147
Key points 148
Key questionsand objectives 149
Further reading: reviews 149
6 Cancer signalling networks 152
Introduction 152
The centralaxis: ARF, MDM2, p53, INK4, RB1 154
MYC and RAS 155
Cancer and cell senescence 156
Tumourigenic DNAviruses 157
Signalling pathwaysthat impact on the centralaxis 158
Cellularresponses during tumourdevelopment 173
Signalling and systems biology 174
Conclusions 175
Key points 176
Key questionsand objectives 176
Further reading: reviews 177
7 The future of cancer prevention, diagnosis and treatment 178
The development of anti-cancer drugs 178
Chemotherapeutic strategies forcancer 180
Drugresistance 186
Non-specific effects 187
The efficacyof chemotherapy 188
Cancer detection: tumourimagingand molecularimaging 188
Molecular imaging 188
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viii Contents
Proteomics 196
Metabolomics 199
Geneexpression profiling 199
Protein imaging 201
Nanotubes, graphene and nanocells 201
Conclusions 204
Key points 204
Key questionsand objectives 205
Further reading: reviews 205
8 The future of cancer in the post-genomic era 209
Human genome sequencing 209
Whole genomesequencing (WGS)and cancer 215
Chromothripsis 218
Genomic partitioning 220
Genome-wide association(GWA)studies and inherited cancer predisposition 223
Therapeuticstrategies for cancer driven by the sequencing revolution 224
Tailoring therapy onthe basisof whole genome sequencing 225
Tumour biomarkers 230
Microfluidicsand the isolationof circulating tumour cells 231
Drugdevelopment 232
The expandingfield of cancer treatment 233
Balancing priorities 236
Conclusions 238
Key points 238
Key questionsand objectives 239
Further reading: reviews 239
Appendix A Tumour grading and staging 241
Appendix B Targets of specificanti-cancerdrugs 245
Appendix C Classesof major oncoproteins 251
Appendix D Major tumoursuppressor genes 253
Appendix E Ten majorcancers ata glance 254
Glossary and abbreviations 276
Bibliography 317
Index 336
A colour plate section isbetweenpagesxxx and xxx.
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ACKNOWLEDGEMENTS
< TOFOLLOW>
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