What is Cancer?
Cancer is a disorder of cell division (leading cause
Cancer = tumor = neoplasm.
Various forms of cancers differ in:
Responsiveness to drugs.
Most common cancers are:
- Lung, colon, rectal.
- Breast (female) & prostate (male).
Characteristics of Cancer Cells:
1. Persistent proliferation & immortality.
Self-sufficiency of growth signals.
Insensitivity to anti-growth signals.
Expression of telomerase.
3. Invasive growth.
4. Formation of metastases.
5. Sustained angiogenesis.
Etiology of Cancer:
Proto-oncogenes: genes that normally
control cell division e.g. bcl-2.
Oncogenes: cancer causing genes.
Tumor suppressor genes: genes that
prevent replication of cells that have
become cancerous e.g. p53.
Malignant transformations occurs
Activation of oncogenes.
Suppression of tumor suppressor genes.
3-7 mutations must occur in a single cell to
Normal functioning immune system
usually recognizes these cells & destroy
Transformation of Proto-oncogenes
to Oncogenes is caused by:
- Chemical carcinogens (cigarette smoking
- Pathogens (hepatitis C virus, H. pylori).
- Radiation (X-rays).
- Hereditary factors.
- Drugs (estrogen).
Stages of Malignant Transformation
Initiation: irreversible DNA damage.
Promotion: cells with genetic defects
(Promoters are substances that enhance
tumor growth by stimulating proliferation,
immune suppression, etc.).
Progression: neoplastic cells →
malignant tumor → invasion of healthy
Tumor can be benign or malignant.
– Invading neighboring tissues.
Describes aggressiveness of cancer cells.
GX: grade cannot be assessed.
G2: moderately differentiated.
G3: poorly differentiated.
Responsiveness of Some
Cancers to Antineoplastic
High: e.g. Hodgkin’s disease, leukemia &
Moderate: e.g. breast, bladder &
Minimal: e.g.e.g. pancreatic, renal,
hepatocellular & colorectal cancer.
The Cell Cycle
G1 = 40%
S = 39%
G2 = 19%
M = 2%
P27: G1-S phases.
P53: G2-M phases.
GF = Proliferating cells (S or M phase)
/resting cells (G0).
Tissues with high % of proliferating cells
have a high growth fraction.
Tissues composed mostly of G0 cells have a
low growth fraction.
Anti-cancer drugs are more toxic to
tissues that have a high growth fraction
(even normal ones).
Why? because they act by disrupting
DNA synthesis or cell division (mitosis).
Accordingly, cells in G0 are resistant to
most anti-cancer therapy.
Solid tumors have a low growth fraction
→ respond poorly.
Disseminated cancers have a high
growth fraction → respond well.
Debulking of tumors: ↓ tumor size by
surgery or radiation →↑ responsiveness to
Recruitment: encouraging resting cells
to enter into the cell cycle (how?).
Cell-Cycle Drug Effects
1. Cell-cycle phase-specific drugs:
Must be present for an extended time →
given by infusions or in frequent small
5-FU acts in S-phase; t½ 15 min.
Administration by prolonged continuous
infusion → ↑ cell kill & improve clinical
Cell-cycle phase non-specific drugs
Act during any phase including G0.
More toxic to proliferating cells than G0
– Cells in G0 often have time to repair
drug-induced damage; whereas
proliferating cells don’t.
Making the Decision to Treat
Goals of therapy:
- Improving survival.
Outcome of therapy depends on:
- General health of patient
- Responsiveness of cancer type (size,
location, grade, etc.).
- Drug resistance.