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

A Concise Journey from Epidemiology through Cell and Molecular Biology to Treatment and Prospects......Page 1
A Concise Journey from Epidemiology through Cell and Molecular Biology to Treatment and Prospects......Page 3
Contents......Page 5
Acknowledgements......Page 9
Introduction......Page 11
Gene nomenclature......Page 15
Incidence......Page 17
Deaths......Page 18
UK and USA......Page 19
Europe......Page 20
The rest of the world......Page 23
Latin America......Page 24
China......Page 25
Africa......Page 26
Age......Page 27
Where do we stand and is there any good news?......Page 29
China......Page 33
Alcohol......Page 34
MYC is a central regulator of cell growth and proliferation......Page 35
Introduction......Page 36
Radiation......Page 37
Ionising radiation......Page 38
Radon......Page 42
Ultraviolet radiation......Page 44
Low-frequency magnetic fields......Page 45
High-frequency magnetic fields (mobile phones)......Page 46
Tobacco......Page 47
Alcohol......Page 49
Diet: epidemiological studies......Page 51
Folate......Page 53
Fibre......Page 54
Obesity......Page 55
Stress......Page 56
Introduction......Page 60
Enzyme-coupled receptors......Page 61
Receptor tyrosine kinases (RTKs)......Page 63
Intracellular signalling from activated tyrosine kinase receptors......Page 65
Activating RAS and MAPK......Page 67
Sustained versus transient activation of RAS and MAPK......Page 69
MYC is a central regulator of cell growth and proliferation......Page 70
MYC and proliferation......Page 73
Cytokine receptors......Page 74
G-protein-coupled receptors......Page 75
Steroid hormones......Page 76
Collecting mutations......Page 82
Genetic roulette......Page 83
The cancer genomic landscape......Page 84
Mutations in `cancer genes´: oncogenes and tumour suppressor genes......Page 85
Oncogenes......Page 86
The first human oncogene......Page 87
What turns a proto-oncogene into an oncogene?......Page 88
A single base change: RAS......Page 89
Other coding mutations: the epidermal growth factor receptor (EGFR)......Page 90
Gene amplification: MYC......Page 91
Chimeric protein: BCR-ABL1, PML-RARA and ETV6-RUNX1......Page 94
Complete loss of a gene......Page 100
Tumour suppressor genes......Page 101
What does the retinoblastoma protein do?......Page 103
Tumour protein 53 (TP53 aka p53)......Page 104
p53, cell cycle arrest, apoptosis and MYC......Page 105
p53 and cancer......Page 106
P53 is not entirely a tumour suppressor......Page 107
DNA repair......Page 108
Hereditary breast cancer......Page 109
Hereditary colon cancer......Page 110
DNA repeats itself......Page 111
Modulating gene expression without mutation: epigenetic changes......Page 112
Micro RNAs (miRNAs)......Page 113
The first human oncogene......Page 117
Introduction......Page 118
Benign tumours......Page 119
The benign-malignant boundary......Page 122
What makes a cancer cell a cancer cell?......Page 123
Cancer cell characteristics......Page 124
Cell growth is largely independent of normal signals......Page 125
Resistance to inhibitory growth signals......Page 126
Resistance to cell death......Page 127
Unlimited replicative capacity......Page 131
Induction of angiogenesis......Page 133
Angiogenic regulators......Page 135
Discovery of angiostatin in a mouse model of metastasis......Page 136
Tumour blood flow and the flexible cancer cell......Page 137
How do cells sense oxygen levels?......Page 140
HIF gives tumour vascular chaos a helping hand......Page 141
The return of Otto Warburg......Page 142
Dormant tumours......Page 146
Inflammation and the immune system......Page 147
The tumour cell environment......Page 148
Primary and malignant tumours......Page 152
Early ideas about metastasis......Page 153
How do tumour cells become metastatic?......Page 154
The epithelial to mesenchymal transition......Page 155
Stem cells......Page 157
How do metastatic tumour cells know where to go?......Page 158
Do metastases metastasise?......Page 161
How does cancer kill you?......Page 162
Introduction......Page 168
The central axis: ARF, MDM2, p53, INK4, RB1......Page 170
MYC and RAS......Page 171
Cancer and cell senescence......Page 172
Tumourigenic DNA viruses......Page 173
Signalling pathways that impact on the central axis......Page 174
Phosphatidylinositol 3-kinase (PI3K): survival and apoptosis signalling......Page 176
Death receptors and the extrinsic pathway of apoptosis......Page 178
The JAK-STAT pathway......Page 179
WNT and GPCR signalling......Page 180
Cell adhesion: cadherin signalling......Page 181
Integrin signalling......Page 182
BCR-ABL1......Page 183
The Hedgehog pathway and GLI signalling......Page 184
Transforming growth factor beta (TGFbeta)......Page 185
Vascular endothelial growth factors (VEGFs) and Notch signalling......Page 187
Cellular responses during tumour development......Page 189
Signalling and systems biology......Page 190
The development of anti-cancer drugs......Page 194
Kinase inhibitors......Page 196
Monoclonal antibodies......Page 197
Anti-angiogenic agents......Page 198
The future of anti-angiogenic agents......Page 199
Liposomal therapy......Page 200
Prophylactic (preventive) vaccines......Page 201
Drug resistance......Page 202
Non-specific effects......Page 203
Positron emission tomography (PET)......Page 204
Magnetic resonance imaging (MRI)......Page 206
13C hyperpolarisation......Page 209
Optical imaging......Page 211
Proteomics......Page 212
Gene expression profiling......Page 215
Nanotubes, graphene and nanocells......Page 217
Headings25......Page 223
Resistance to cell death......Page 224
Human genome sequencing......Page 225
Whole genome sequencing (WGS) and cancer......Page 231
Chromothripsis......Page 234
Genomic partitioning......Page 236
Genome-wide association (GWA) studies and inherited cancer predisposition......Page 239
Therapeutic strategies for cancer driven by the sequencing revolution......Page 240
Tailoring therapy on the basis of whole genome sequencing......Page 241
BRAF......Page 242
PI3K......Page 243
MYC......Page 244
p53......Page 245
Tumour biomarkers......Page 246
Microfluidics and the isolation of circulating tumour cells......Page 247
Drug development......Page 248
The expanding field of cancer treatment......Page 249
Balancing priorities......Page 252
Appendix A: Tumour grading and staging......Page 257
Tumour staging......Page 258
Examples......Page 259
Appendix B: Targets of specific anti-cancer drugs......Page 261
Class 6 Cell cycle regulators......Page 267
Class 8 Intracellular membrane factor......Page 268
Appendix D: Major tumour suppressor genes......Page 269
Lung cancer......Page 270
Carcinoid......Page 271
Tracheal cancer......Page 272
Stomach (gastric) cancer......Page 273
Liver cancer......Page 274
Colorectal cancer (colon cancer, large bowel cancer)......Page 275
Breast cancer......Page 276
Oesophageal cancer......Page 279
Cervical cancer......Page 281
Pancreatic cancer......Page 283
Prostate cancer......Page 284
Leukaemia......Page 285
Bibliography......Page 292
Appendix A......Page 333
Tumour vascularisation......Page 338
The return of Otto Warburg......Page 339
Inflammation and the immune system......Page 340
Stem cells......Page 341
Phosphatidylinositol 3-kinase (PIK3): survival and apoptosis signalling......Page 342
Integrin signalling......Page 343
Signalling and systems biology......Page 344
Positron emission tomography (PET)......Page 345
Metabolomics......Page 346
Burkitt´s lymphoma......Page 347
Whole genome sequencing (WGS) and cancer......Page 348
BRAF......Page 349
Drug development......Page 350
Tumour staging......Page 351
Index......Page 352