Selected cell and selective microenvironment in neoplastic development.

Recent analysis of genetic alterations in human cancer points to a major role for selection in neoplastic development but provides few details about the dynamics of the process. Many such details, however, have emerged from quantitative studies of spontaneous transformation among mammalian cells in culture. The chief insight of these studies is that there is a continuous generation of variants in proliferative potential among growing cells that provides the substratum for progressive development to a frankly neoplastic state when selective growth conditions are persistently applied. Much of the selection occurs before the cells are capable of producing discrete neoplastic foci. The varied observations in cell culture draw attention to analogous features of carcinogenesis in experimental animals and the development of human cancer.