Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

TumorigenesisTumorigenesis

Initialgenetic change

(eg, loss of function of pRb or overexpression of c-myc)

Decreasein apoptoticcell death

Subsequentgenetic change

Normalcell

Increase incell proliferationand apoptotic

cell death

Secondarygenetic change

(eg, dysfunction of p53or overexpression of bcl-2)

Further alterationsin phenotype(eg, invasivenessand metastasis)

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology Emergence of tumor cell Emergence of tumor cell

heterogeneityheterogeneity

Primary NeoplasmPrimary Neoplasm MetastasesMetastases

TRANSFORMATIONTRANSFORMATION TUMOR EVOLUTIONTUMOR EVOLUTION METASTASISMETASTASIS TUMOR EVOLUTIONTUMOR EVOLUTIONAND PROGRESSIONAND PROGRESSION AND PROGRESSIONAND PROGRESSION

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology Host influences on metastatic Host influences on metastatic

diseasedisease

Anatomical factors

Organ microenvironment

Angiogenic factors

Immune response

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology Cancer cells vs normal cellsCancer cells vs normal cells

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology Precancerous conditionsPrecancerous conditions

Neoplasia (eg, prostatic intraepithelial neoplasia)

Polyps (eg, adenomatous polyps)

Carcinoma in situ

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

The role of oncogenesThe role of oncogenes

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

PathogenesisPathogenesis

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

AngiogenesisAngiogenesisEstablishment 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)]

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

Cell cycleCell cycle

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

The doubling processThe doubling process

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

Tumor growth and detectionTumor growth and detection

10101212

101099

timetime

DiagnosticDiagnosticthresholdthreshold

(1cm)(1cm)

UndetectableUndetectablecancercancer

DetectableDetectablecancercancer

Limit ofLimit ofclinicalclinical

detectiondetection

HostHostdeathdeath

Nu

mb

er o

fN

um

ber

of

can

cer

cells

can

cer

cells

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Cancer Biology

Dormancy of tumor cellsDormancy 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 phaseRate of cell death counterbalances rate of cell

division