On October 23rd, 2014, we updated our
By continuing to use LinkedIn’s SlideShare service, you agree to the revised terms, so please take a few minutes to review them.
ONCOLOGY Cancer biology Tumorigenesis Kastan MB. Cancer: Principles & Practice of Oncology. 5th ed. 1997;121-134. Initial genetic change (eg, loss of function of pRb or overexpression of c-myc) Decrease in apoptosic cell death Subsequent genetic change Normal cell Increase in cell proliferation and apoptosic cell death Secondary genetic change (eg, dysfunction of p53 or overexpression of bcl-2) Further alterations in phenotype (eg, invasiveness and metastasis)
ONCOLOGY Cancer biology Emergence of tumor cell heterogeneity Primary Neoplasm Metastases TRANSFORMATION TUMOR EVOLUTION METASTASIS TUMOR EVOLUTION AND PROGRESSION AND PROGRESSION
Host influences on metastatic disease Fidler IJ. Cancer: Principles & Practice of Oncology. 5th ed. 1997;135-147.
ONCOLOGY Cancer biology CANCER CELLS NORMAL CELLS Loss of contact inhibition Increase in growth factor secretion Increase in oncogene expression Loss of tumor suppressor genes Neovascularization Oncogene expression is rare Intermittent or coordinated growth factor secretion Presence of tumor suppressor genes Frequent mitoses Nucleus Blood vessel Abnormal heterogeneous cells Normal cell Few mitoses Cancer cells vs normal cells
Precancerous conditions Stedman’s Medical Dictionary. 26th ed. 1995;1182,1405, 279.
ONCOLOGY Cancer biology Growth factor Growth factor receptor Paracrine (adjacent cells) Growth factor and receptor synthesis Post receptor signal transduction pathways Gene activation Oncogenes Autocrine stimulation The role of oncogenes
ONCOLOGY Cancer biology Pathogenesis TRANSFORMATION ANGIOGENESIS MOTILITY & INVASION Capillaries, Venules, Lymnphatics ADHERENCE ARREST IN CAPILLARY BEDS EMBOLISM & CIRCULATION EXTRAVASATION INTO ORGAN PARENCHYMA RESPONSE TO MICROENVIRONMENT TUMOR CELL PROLIFERATION & ANGIOGENESIS METASTASES METASTASIS OF METASTASES TRANSPORT Multicell aggregates (Lymphocyte, platelets)
ONCOLOGY Cancer biology
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)]
Angiogenesis Fidler IJ. Cancer: Principles & Practice of Oncology. 5th ed. 1997;135-147.
ONCOLOGY Cancer biology Cell cycle CELL DIFFERENTIATION CELL LIFE CYCLE TIME CELL DIVISION G 2 PERIOD (CHROMOSOME REPLICATION) S-PHASE G 1 PERIOD
ONCOLOGY Cancer biology The doubling process Normal cell Dividing Malignant transformation 2 cancer cells Doubling 4 cells Doubling 8 cells Doubling 16 cells 1 million cells (20 doublings) undetectable 1 billion cells (30 doublings) lump appears 1 trillion cells (40 doublings – 2 lb/1kg) 41 – 43 doublings — Death
ONCOLOGY 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
ONCOLOGY Cancer biology
Malignant tumor cells can remain dormant yet viable for years
Emergence from dormancy can lead to disease recurrence
Cells may arrest in G 0 phase
Rate of cell death counterbalances rate of cell division
Dormancy of tumor cells Fidler IJ. Cancer: Principles & Practice of Oncology. 5th ed. 1997;141.