Tumourigenesis: the subterfuge of selection.

Variation of rearrangement of regulatory genes is responsible for cellular malignant change. These types of chromosomal variations also produce heterochrony or paedomorphic evolution at the organismal level. Analogously, neoplasia represents a cellular 'macroevolutionary' event, and a tumour can be said to be an evolved population of cells. To understand this cellular evolution to malignancy, it may be necessary to go beyond a 'clonal selection' (adaptationist) explanation of neoplastic alteration. In the pericellular environment 'natural selection' consists of the organizational restraints of surrounding cells as well as the host's immunological surveillance and non-specific monocyte-macrophage systems. Indirect evidence suggests that success for the neoplasm depends not upon 'clonal selection', but solely upon a genetic methodology-the function of which is to elude selection. The author has coined the term 'cellular heterochrony' to illustrate analogic similarities in the molecular modes of speciation between anaplastic cancer cells and the heterochronic evolution of organisms. By reverting to juvenile (embryonic) repertoire of cellular behaviour a tumour secures its own tenure or niche by usurping the host's armamentarium of selection forces, employing many of the same or similar methods by which implanting and invading tissues of the mammalian embryo forestall maternal detection and rejection. A number of ways by which the tumour blocks, subverts or evades selection are discussed.