Pathogenesis of Cancer Flashcards
(10 cards)
1
Q
Describe the difference between benign and malignant tumours
A
Benign - non-invasive but hyper-proliferative
Malignant - able to invade local tissues
2
Q
Outline the barriers that exist in cells to prevent the development of
cancer
A
- Growth factor regulation
- Antiproliferative signals
- Cell life
- finite devisions (Hayflick number)
- balance of positive and negative signalling proteins
- immune system
3
Q
Breach #1 - self sufficient growth signals
A
- Cancer cells can divide with low growth factors or produce their own
- oncogene activation allows for these cells to produce their own growth factor
4
Q
Breach #2- insensitivity to growth inhibition
A
- Growth factors → activate Cyclin/CDK complexes
→ phosphorylate Rb+++ → releases E2F → cell cycle progresses G1→S
5
Q
Breach #3 - evasion of apoptosis
A
- Hormone receptor (Estrogen R & Androgen R) expression ↑ - survival signal
- Anti-apoptotic protein expression levels ↑
- mutations of the p53 TSG
6
Q
Breach #4 - Cell immortalisation
A
- Re-expression of telomerase is used to immortalise cells
- telomerase transcribes 6bp
telomere repeats at the end of telomeres - typically only expressed in utero
- 85-90% tumours ↑ telomerase expression
7
Q
Breach #5 - angiogenesis
A
- Involves many +’ve and –’ve signals:
o positive - e.g. vascular endothelial GF (VEGF)
o negative - e.g. thrombospondin-1 (Tsp) - Shift in the balance of signalling proteins (VEGF↑, Tsp-1↓) → angiogenesis
8
Q
Breach #6 - Tissue invasion and distant metastasis
A
- Cancer deaths are rarely due to primary tumour growth
- Spread to distant sites causes ~90% of cancer deaths
9
Q
Breach #7 - Evasion of the immune system
A
- They co-opt immune cells to ↑growth & encourage invasion
- Tumor associated macrophages: promotes the growth of tumor cells
- T-cell regulators: prevent the action of T-cells
10
Q
Know some common mutations that help cancers break through the barriers
A
- P53 tumor supressor gene mutation
