Cancer: the evolved consequence of a destabilized genome.

The genome is a stable repository of vastly intricate genetic information developed over eons of evolution; this information is replicated at the highest fidelity and expressed within each cell at the highest selectivity. Non-leukemia cancers break this standard; the intricate genetic information qualitatively and progressively deteriorates, resulting in a somatic Darwinian free-for-all. In a process lasting several years, a genomically heterogeneous population replicates from a single cell that originally lost the ability to preserve its genomic integrity. Cells selected for their abilities to proliferate and spread, while evading host defenses, inexorably expand their numbers. The clinical consequences of this become severe, as the genomically diverse cell population that evolves contains members that can evade most therapeutic approaches aimed at "the tumor cell". Copyright 2001 John Wiley & Sons, Inc.