1. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Cancer Biology

2. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Tumorigenesis Cancer Biology Tumorigenesis Initial genetic change (eg, loss of function of pRb or overexpression of c-myc) Decrease in apoptotic cell death Subsequent genetic change Normal cell Increase in cell proliferation and apoptotic cell death Secondary genetic change (eg, dysfunction of p53 or overexpression of bcl-2) Further alterations in phenotype (eg, invasiveness and metastasis)

3. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Emergence of tumor cell heterogeneity Cancer Biology Emergence of tumor cell heterogeneity Primary NeoplasmMetastases TRANSFORMATIONTUMOR EVOLUTIONMETASTASISTUMOR EVOLUTION AND PROGRESSIONAND PROGRESSION

4. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Host influences on metastatic disease Cancer Biology Host influences on metastatic disease Anatomical factors Organ microenvironment Angiogenic factors Immune response

5. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Cancer cells vs normal cells Cancer Biology Cancer cells vs normal cells

6. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Precancerous conditions Cancer Biology Precancerous conditions Neoplasia (eg, prostatic intraepithelial neoplasia) Polyps (eg, adenomatous polyps) Carcinoma in situ

7. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria The role of oncogenes Cancer Biology The role of oncogenes

8. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Pathogenesis Cancer Biology Pathogenesis

9. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Angiogenesis Cancer Biology Angiogenesis Establishment of a capillary network from the surrounding host tissue A series of processes originating from microvascular endothelial cells Mediated by multiple molecules released by both tumor and host cells [eg, fibroblastic growth factor (FGF), vascular endothelial growth factor (VEGF), vascular permeability factor (VPF), angiogenin, epidermal growth factor (EGF)]

10. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Cell cycle Cancer Biology Cell cycle

11. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria The doubling process Cancer Biology The doubling process

12. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Tumor growth and detection Cancer Biology Tumor growth and detection 10 12 10 9 time Diagnostic threshold (1cm) Undetectable cancer Detectable cancer Limit of clinical detection Host death Number of cancer cells

13. Clinical Division of Oncology Department of Medicine I Medical University of Vienna, Austria Dormancy of tumor cells Cancer Biology Dormancy of tumor cells Malignant tumor cells can remain dormant yet viable for years Emergence from dormancy can lead to disease recurrence Possible mechanisms: Cells may arrest in G0 phase Rate of cell death counterbalances rate of cell division