Published in Cancer Detection and Prevention 1993; 17(6):567-573.

Multistage Carcinogenesis - Genetic and Epigenetic Mechanisms in Relation to Cancer Prevention

Henry C. Pitot, M.D., Ph.D.

McArdle Laboratory for Cancer Research, Departments of Oncology and Pathology, The Medical School, University of Wisconsin, Madison, WI 53706

ABSTRACT: The prevention of cancer is, at our present state of knowledge, the most effective and inexpensive mode of controlling this disease. Passive cancer prevention is practiced voluntarily or, in part, through governmental regulation in many parts of the world. However, active cancer prevention by the administration of vaccines, dietary factors, antihormones, or other agents is likely to be the most effective mechanism of cancer prevention in humans. Carcinogenesis develops in three defined stages-initiation, promotion, and progression-the first and third resulting from irreversible genetic changes in the cell, whereas the intermediate stage of promotion involves an epigenetic alteration of the expression of the genome and cell division. Thus, the stage of promotion is the most effective site to target for both active and passive cancer prevention. A review of the modalities presently used in cancer prevention, both active and passive, demonstrates that all such methods involve an inhibition and/or reversal of this intermediate stage, thus preventing the development of the malignant process. Future advances in cancer prevention will depend on better knowledge of the mechanisms of the stages of carcinogenesis in order that rational preventive agents and formats may be used in altering or modifying the appropriate stage(s) of neoplastic development.

KEY WORDS: multistage carcinogenesis, initiation, promotion, progression.