The evolutionary origin of genetic instability in cancer development

The standard model of carcinogenesis is currently being questioned. The main controversy concerns genetic instability and has links to fundamental questions in evolutionary biology. This paper aims to clarify the underlying conflict between the linear configuration of the standard model and the non-linear dynamics of Darwinian evolution. It addresses the problem of applying the concept of clonal selection to genetically unstable cells and presents an alternative perspective based on the principles of molecular evolution. This model explains genetic instability in terms of competition between genetic strategies and draws lines to basic aspects of evolutionary biology. (C) 2004 Elsevier Ltd. All rights reserved.