Clonal evolution
Clonal evolution is the model of cancer progression in which a tumor is a population of cells descended from a single common ancestor, within which heritable variation arises continuously and selection determines which lineages expand. Peter Nowell proposed it in 1976.
The model
Two ingredients drive the process:
- Variation. Genomic instability, replication errors, and environmental damage generate genetically diverse cells. Mutation supply sets the rate at which a tissue samples new variants.
- Selection. The microenvironment — resources, stroma, immune pressure, therapy — determines which variants expand. A clone that grows faster, resists death, or recruits blood supply expands at the others’ expense.
Progression is the repeated application of this cycle:
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