01Darwin inside a tumor
In 1976 Peter Nowell described cancer as an evolutionary process: mutations create variation, and selection favors cells that grow faster or survive better. Over time, successive clones sweep through the tumor.
The result is intratumoral heterogeneity — different regions of the same tumor carry different mutations. A biopsy from one spot may miss a resistant subclone elsewhere.
02Consequences for treatment
Therapy is a powerful selective pressure. A drug that kills 99.9% of cells may leave a pre-existing resistant clone to regrow. That's why combination therapy and monitoring with liquid biopsy (circulating tumor DNA) are increasingly used.
Cancer stem cells add another layer: in some tumors a subpopulation with self-renewal capacity may survive treatment and reseed growth.