Molecular biology of cancer

What causes cancer?

Genetic mutation - activation of oncogenes and inactivation of tumour suppressor genes cause genetic instability = more mutations

What are the hallmarks of cancer?

1. Self-sufficiency in growth signals

2. Insensitivity to antigrowth signals

3. Evasion of apoptosis

4. Limitless replicative potential

5. Sustained angiogenesis

6. Tissue invasion & metastasis

7. reprogramming of energy metabolism

8. Evasion of immune destruction

What are the phases of the cell cycle?

G1: gap 1

S: synthesis

G2: gap 2

M: mitosis

G0: arrest

G1 - gap 1

No visible changes, but increase in cell contents (organelles, proteins, etc) including replication machinery

M -mitosis

Segregation of chromosomes, followed by division to produce two daughter cells. Visually striking, but short

s - synthesis

Replication of DNA occurs, resulting in chromosomes becoming two sister chromatids attached at the centromere.

G2- gap 2

No visible changes, preparation for division process

G0

Stage of cells not going through the cell cycle. Cells may be able to return to the cell cycle and divide, or may be unable to do so (“post- mitotic”, e.g. neurons or cardiomyocytes)

What is responsible for making sure processes occur in the right order?

Cyclin-CDK (cyclin dependant kinase) complexes and regulators

• CDK inhibitors, Cdc25 phosphatases)

• Cyclin-CDK complexes signal stages of cycle

What controls if cells divide at all?

• transition points - checkpoint pathways monitor conditions & can transiently halt the cell cycle if it isn’t suitable