Table of contents for Molecular biology of human cancers : an advanced student's textbook / by Wolfgang Arthur Schulz.


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PART I - MOLECULES, MECHANISMS, AND CELLS
1 An Introduction to Human Cancers .............................................. ...............   1
1.1 An overview of the cancer problem................................................................ 1
1.2  Causes  of  cancer....................................................................... ................ 5
Box 1.1 Reactive oxygen species ................................................. ............ 10
1.3 Characteristic Properties of Cancers and Cancer Cells.............................. 11
Box 1.2: Hallmarks of Cancer .................................................................. 18
1.4 Characterization and Classification of Cancers in the Clinic................... 17
1.5  Treatment of  Cancer.................................................................................... 21
Further  reading............................................................................................... 23
2 Tumor Genetics ................................................................................................ 25
2. 1 Cancer as a genetic disease.................................................................. ..  26
2.2. Genetic alterations in cancer cells......................................... ............ ... 27
2.3 Inherited predisposition to cancer..................................................................  37
2.4  Cancer  genes  ............................................................................................ 42
2.5 Accumulation of genetic and epigenetic changes in human cancers........... 44
Further  reading......... ........................ ............................................................. 45
Box 2.1 Tumor viruses in human cancers ....................................... .......... .. 46
3 DNA Damage and DNA Repair ........................................................................ 47
3.1 DNA damage during replication: base excision and nucleotide excision
repair ............................... ...................... .................................... ......... 4 8
3.2 Nucleotide excision repair and crosslink repair ........................................ 55
3.3  Strand-break  repair.......................................................................... ......... 62
3.4 Defects in DNA repair and cancer susceptibility........................................... 66
3.5 Cell protection mechanisms in cancer.......................................................... 68
Further  reading............................................................................................... 70
4 Oncogenes........................................................................................................ 71
4.1  Retroviral oncogenes........................................................................ ........ 72
4.2 Slow-acting transforming retroviruses.................................... ............ 75
4.3 Approaches to the identification of human oncogenes..............................  . 78
4.4 Functions of human oncogenes ............................................... ............ 84
Further  reading...............................................................................................  89
Box 4.1 Carcinogenesis by HTLV-I.................................................................. 90
5 Tumor Suppressor Genes ........................................................................... 91
5.1 Tumor suppressor genes in hereditary cancers.......................................... 92
5.2  RB1  and  the  cell cycle........................................................................ ........ 97
5.3 TP53 as a different kind of tumor suppressor ............................................  101
5.4   Classification         of tumor suppressor genes...................................................                    109
Further reading.....................................................               ...................................... 111
Box     5.1 Human         papilloma viruses..................................................................... 112
6 Cancer Pathways ................................................................................................ 113
6. 1 Cancer Pathways.....................................................................................                    114
6.2 MAPK          signaling      as a cancer pathway               ....................................................... 115
6.3   The PI3K        pathway       ..................................................................................   ... 119
6.4 Regulation of the cell cycle by the MAPK and PI3K pathways ............... 123
6.5 Modulators of the MAPK                     and P13K pathways........................................... 126
6.6   The    TP53 network...........................................................................            ......... 129
6.7 Signaling         by   TGFP/       factors ........................................................................ 131
6.8 Signaling         through STA Tfactors ................................................................. 132
6.9   The NFIcB        pathway........................................................................         ......... 135
6.10 Developmental regulatory  systems as cancer pathways ............................ 137
Further reading................................................................................................... 144
7 Apoptosis and Replicative Senescence in  Cancer............................................ 145
7.1 Limits to cell proliferation................................................................                   .... 146
7.2 Mechanisms of apoptosis.............................................................................. 150
7.3 Mechanisms of diminished    apoptosis in cancer........................................... 156
7.4 Replicative senescence and  its disturbances in  human cancers................... 159
Further reading................................................................................................... 164
Box     7.1: Human  aging and cancer..................................................................... 165
8 Cancer Epigenetics ........................................                   ................................................. 167
8.1 Mechanisms of epigenetic inheritance ....................................................... 168
8.2 Imprinting and X-inactivation .................................................................                  170
8.3 DNA  methylation .................................................................................... 174
8.4   Chromatin structure...................................................................................... 179
8.5 Epigenetics of cell differentiation............................................................... 182
8.6 Epigenetics of tissue homeostasis............................................................... 185
Further reading................................................................................................... 191
Box 8.1 Carcinogenesis by HIV                                                                                               192
9 Invasion and    metastasis ................................................................................. 193
9.1 Invasion and metastasis as multistep   processes........................................... 194
9.2 Genes and proteins involved in cell-to-cell and cell-matrix adhesion......... 197
9.3 Genes and proteins involved in extracellular matrix remodeling
during      tumor invasion.....................................................................            ....      202
9.4 Angiogenesis .............................................................................................. 206
9.5 Interactions of invasive tumors with the immune system              ........................... 210
9.6   The importance of tumor-stroma    interactions............................................ 212
Further reading ................................................................................................ 216
Box     9.1 Tumor hypoxia and  its consequences ................................................ 217
PART II - HUMAN CANCERS
10 Leukemias and Lymphomas............................................................................ 219
10.1 Common properties of hematological cancers......................................... 221
10.2 Genetic aberrations in leukemias and lymphomas................................... 223
10.3 Molecular biology ofBurkitt lymphoma................................................... 226
10.4 Molecular biology of CML ....................................................................... 232
10.5 Molecular biology of PML ....................................................................... 237
F urther  reading ................................................................................................... 242
11 Wilms Tumor (nephroblastoma) .................................................................. 243
11.1 Histology, etiology and clinical behavior of Wilms tumors....................... 244
11.2 Genetics of Wilms tumors and the WTI gene........................................ . 246
11.3 Epigenetics of Wilms tumors and the 'WT2' locus................................... 250
11.4 Towards an improved classification of Wilms tumors ............................. 252
Further  reading  ................................................................................................ 253
12 Cancers of the skin .......................................................................................  255
12.1 Carcinogenesis in the skin............................................................... ... 256
12.2 Squamous cell carcinoma................................................................... 260
12.3  Basal Cell Carcinoma.................................................................... .....  262
12.4  Melanoma  .................................................................................................. .   266
12.5  Tumor  antigens....................................................................................... 269
F urther  reading  ................................................................................................... 270
13 Colon Cancer       ..........................................                        271
13. 1 Natural history of colorectal cancer .......................................................  272
13.2 Familial Adenomatous Polyposis Coli and the WNT pathway ................ 273
13.3 Progression of Colon Cancer and the Multi-Step Model
of  Tumorigenesis............................................................................ ......... 280
13.4 Hereditary nonpolyposis colon carcinoma .............................................. 282
13.5 Genomic instability in colon carcinoma................................................... 284
13.6 Inflammation and colon cancer................................................................ 285
Further  reading .................................................................................................. 287
Box 13.1 Positional cloning of tumor suppressor genes in hereditary cancers.288
14 Bladder Cancer .........................................                             289
14.1 Histology and etiology of bladder cancer ................................................ 290
14.2 Molecular alterations in invasive bladder cancers.................................. 297
14.3 Molecular alterations in papillary bladder cancers ................................ 302
14.4 A comparison of bladder cancer subtypes................................................ 304
Further  reading.................................................................................................. 305
Box 14.1: Tumor suppressor candidates at 9q in bladder cancer ...................... 306
15 Renal Cell Carcinoma ........................................................................  307
75.1 The diversity of renal cancers .................................................................. 308
15.2 Cytogenetics of renal cell carcinomas...................................................... 310
15.3    Molecular biology  of   inherited       kidney     cancers .............................................. 311
15.4 Von-Hippel-Lindau syndrome and renal carcinoma.................................. 316
15.5    Molecular biology  of clear cell renal carcinoma..................................... 321
15.6 Chemotherapy and immunotherapy of renal carcinomas .......................... 324
Further reading ................................................................................................... 326
16   Liver Cancer ..................................................................................................... 327
16.1 Etiology of liver cancer .............................................................................. 328
16.2    Genetic changes in  hepatocellular carcinoma........................................... 331
16.3     Viruses in HCC........................................................................................... 336
Further reading................................................................................................ 339
Box     16.1 Hepatocellular carcinoma in  experimental animals........................... 340
17   Stomach     Cancer .....................................................................................341
17.1 Etiology of stomach          cancer ...................................................................... 342
17.2    Molecular mechanisms in gastric cancer................................................. 345
17.3 Helicobacter pylori and  stomach        cancer.................................................. 348
Further reading................................................................................................... 354
Box      17.1: Barrett esophagus and  esophageal cancer......................................... 355
18   Breast Cancer .................................................................................................... 357
18.1 Breast biology ........................................................................................... 358
18.2 Etiology of breast cancer.................................................................                   ... 364
18.3 Hereditary  breast cancer............................................................................. 365
18.4 Estrogen  receptors and ERBB proteins in breast cancer........................... 373
18.5    Classification  of breast cancers ...............................................................                  378
Further reading:.................................................................................................. 382
19   Prostate Cancer ................................................................................................ 383
19.1 Epidemiology   of prostate cancer............................................                  .................. 384
19.2 Androgens in prostate cancer................................................................                                  389
19.3    Genetics and epigenetics ofprostate cancer.............................................. 394
19.4    Tumor-stroma interactions in prostate cancer......................................... 398
Further reading................................................................................................... 402
PART III - PREVENTION, DIAGNOSIS, AND THERAPY
20   Cancer Prevention ............................................................................................ 403
20.1     The importance of cancer prevention....................................................... 403
20.2 Primary prevention...............................................................................                         ... 404
20.3     Cancer prevention and    diet ...................................................................... 408
20.4 Prevention of cancers in groups at high risk............................................ 415
20.5 Prevention ofprostate cancer by screening the aging male population.... 420
20.6     Other types ofprevention                   ......................................................................... 423
Further reading................................................................................................... 426
21 Cancer Diagnosis .............................................................................................. 427
21.1 The evolving scope of molecular diagnostics........................................... 427
21.2 Molecular diagnosis of hematological cancers.......................................... 429
21.3 Molecular detection of carcinomas .......................................................... 433
21.4 Molecular classification of carcinomas ................................................. 439
21.5 Prospects of molecular diagnostics in the age of individualized therapy.. 442
Further  reading  ............................................. .................................................  447
22 Cancer Therapy ................................................................................................ 449
22.1 Limitations of current cancer therapies .............................................. 449
22.2 Molecular mechanisms of cancer chemotherapy ....................................... 450
22.3 Principles of targeted drug therapy ........................................................... 459
22.4 Examples of new target-directed drug therapies ........................................ 464
22.5 New concepts in cancer therapy: Immunotherapy ..................................   475
22.6 New concepts in cancer therapy: Gene therapy..........          .............................. 479
22. 7 The future of cancer therapy ..................................................... ............... 486



Library of Congress subject headings for this publication: Cancer Molecular aspects, Cancer Molecular diagnosis, Cancer Genetic aspects, Neoplasms microbiology, Neoplasms genetics