Perspective on Multistage Nature of Carcinogenesis

cell population, and with each step, the process shows an increased probability of evolving ultimately into a malignant neoplastic population. Thus, the carcinogenic process (with many types of etiological agents) appears to be one of cellular evolution (23) based upon repeated selection of rare cells (4, 31,57), with increasing relevance to cancer as the system evolves through the noncancerous steps. It must be emphasized that the different cell populations that constitute the long precancerous period show no evidence of cancer and that the appearance of cells with any properties of cancer is very late in the process. Once a malignant neoplastic cell population does appear, its further progression is most easily understood as a manifestation of repeated new clonal selections for increasing growth rate and autonomy (4, 57). The term "neoplastic" is applied selectively to