Role of Apoptosis in Carcinogenesis

Apoptosis

Apoptosis, or programmed cell death, is a natural mechanism to eliminate damaged or unwanted cells.
In cancer, the cancer cells evade apoptosis, allowing survival despite DNA damage or oncogenic stress.

Apoptosis removes damaged or unwanted cells in our body.
In normal physiology it prevents survival of cells with DNA damage.
In Cancer, due to defective apoptosis the mutated cells are able to survive.
Normally p53 plays a central role by inducing cell cycle arrest (via p21) and triggering apoptosis if DNA damage is irreparable.
But in cancer this role is altered and there is loss of p53, resulting in loss of apoptosis of damaged cells.
There is also overexpression of anti-apoptotic proteins (e.g. Bcl-2) in cancer.
There is also downregulation of pro-apoptotic proteins (e.g. bax)

Accumulation of genetically unstable cells → malignant transformation

Mutation or loss of pro-apoptotic genes:
- Example: p53 mutation (prevents apoptosis in response to DNA damage).
Overexpression of anti-apoptotic proteins:
- Example: BCL-2 overexpression in B-cell lymphomas.
Downregulation of death receptors:
- e.g. decreased Fas (CD95) receptor expression.
Disruption of intrinsic (mitochondrial) apoptotic pathway:
- Prevents release of cytochrome c, blocking caspase activation.