Cancer Biology

M-S Maira, M A Pearson, D Fabbro, and C García-Echeverría, Novartis Institutes for BioMedical Research, Basel, Switzerland

© 2007 Elsevier Ltd. All Rights Reserved.

7.01.1 Introduction 2

7.01.2 Cancer Epidemiology 2

7.01.2.1 Molecular Cancer Epidemiology 3

7.01.2.2 Risk Factors and Cancer 3

7.01.2.3 Cancer Screening, Diagnosis, and Prevention 5

7.01.2.3.1 Genetic markers 5

7.01.2.3.2 Diagnostic and prognostic biomarkers 5

7.01.3 Available Treatment Modalities 6

7.01.3.1 Surgery 6

7.01.3.2 Chemotherapy 6

7.01.3.3 Radiotherapy 7

7.01.3.4 Photodynamic Therapy 7

7.01.4 Treatment Options for Major Cancers and Future Directions 7

7.01.5 Cell Proliferation, Differentiation, and Apoptosis 9

7.01.5.1 The Cell-Cycle and Cancer 9

7.01.5.1.1 The G1/S transition and the increase of activity of cyclin-dependent kinases 9

7.01.5.1.2 The G2/M transition, control of deoxyribonucleic acid (DNA) damage, and the spindle checkpoint 11

7.01.5.2 Differentiation: Tumor versus Normal Cells 12

7.01.5.3 Apoptosis 13

7.01.5.3.1 Intrinsic and extrinsic apoptosis pathways 13

7.01.5.3.2 Defects of the apoptosis machinery in cancer cells 13

7.01.6 Invasion and Metastasis 14

7.01.6.1 Invasive Growth and the Tumor Microenvironment 14

7.01.6.2 Adhesion Molecules 14

7.01.6.3 Cadherins and epithelial-mesenchymal transition (EMT) 15

7.01.6.4 Integrins and Downstream Signaling Pathways 15

7.01.6.5 Integrins in Extracellular Matrix Remodeling and Invasion 16

7.01.6.6 Integrins and Angiogenesis 16

7.01.6.7 Proteolytic Enzymes and the Invasive Process 16

7.01.6.8 Metalloproteinase Family 17

7.01.6.9 Plasminogen Activation and Cancer 17

7.01.6.10 Growth of Tumor Cells at Secondary Sites 18

7.01.6.11 Tumor Necrosis Family: Apoptosis and Immune Surveillance 18

7.01.7 Tumor Angiogenesis 19

7.01.7.1 Vascular Endothelial Growth Factor 19

7.01.7.2 Regulators of Vascular Endothelial Growth Factor-A and Vascular

Endothelial Growth Factor Receptor Expression 20

7.01.7.3 Fibroblast Growth Factor and Angiogenesis 21

7.01.7.4 Platelet-Derived Growth Factor 21

7.01.8 Growth Factor Signal Transduction in Cancer 22

7.01.8.1 Deregulated Receptor Tyrosine Kinases 22

7.01.8.1.1 Epidermal growth factor receptors 22

7.01.8.1.2 Oncogenic activation of c-Kit 22

7.01.8.2 Deregulated Cytosolic Signaling Pathways 23

7.01.8.2.1 The Ras-Raf-MEK-MAPK pathway 23

7.01.8.2.2 The phosphatidylinositol-3-kinase-PDK1-protein kinase B pathway 23 References 24

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