Neoplastic development, process

It has seemed pretty clear for several decades, from both studies in humans and in experimental settings, that carcinogenesis is a multistage process. At the broadest level, the process can be thought of as one in which a normal cell is first converted to a permanently deranged cell, which is called a neoplastic cell, and a second sequence in which the neoplastic cell develops into a tnmor, a neoplasm, that the pathologist can observe neoplastic conversion and neoplastic development. 

Cancer chemoprevention refers to the administration of chemical agents to prevent the initiational (mutational) and promotional events that occur during the process of neoplastic development (carcinogenesis). The initiation involves the direct action of the carcinogen on target cells (or after his metabolic activation) whereas promotion and/ or progression means that the initiated cells are stimulated to proliferate. 

The multi-hit models are most suitable for extrapolating the effect of genotoxic substances. It is implicit in these models that aU hits occur in one specific cell that only begins to divide and develop into a tumor when it has received the necessary number of hits. However, this is in poor agreement with experimental data, which show that prohferation of the cells that have had their first hit (the initiated cells) into pre-neoplastic lesions considerably increases the risk of a second hit in an initiated cell. While the one-hit model often oversimplifies the process, the multi-hit models impose an unreasonable tight restriction of the possibdity of more than one critical hit affecting the same cell. 

The development of drugs with actions on intermediary metabolism of proliferating cells has been important both clinically and conceptually. While biochemical properties unique to all cancer cells have yet to be discovered, neoplastic cells do have a number of quantitative differences in metabolism from normal cells that render them more susceptible to a number of antimetabolites or structural analogs. Many of these agents have been rationally designed and synthesized based on knowledge of cellular processes, and a few have been discovered as antibiotics. 

Cancer chemoprevention can be defined as the prevention of neoplastic diseases by providing people with one or more chemical substances in the form of special preparations or as naturally occurring dietary components. Cancer development is a slow, multistage process that takes about 20 years on average. The number of new cancer cases estimated around the world for only 25 different cancers in 1990 amounted to 8.1 million (Parkin, 1998). If this number is multiplied by 20 years of latent development, it may be expected that more than 160 million people are, at this moment, at one of the stages of neoplastic transformation, which is life threatening. These people are the target population of cancer prevention, thus chemoprevention. 

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