Strategies for inhibiting multistage carcinogenesis based on signal transduction pathways

It is obvious that the simplest approach to cancer prevention is to avoid exposure to causative agents, whether they be tumor initiators, promoters, or agents that enhance the progression of cells to increasing degrees of malignancy. On the other hand, this simple approach will not always be feasible, either because the causative agent cannot be readily removed from the environment, the precise agent is not known with certainty, or individuals have already suffered significant exposure. It is necessary, therefore, to develop new strategies that can arrest or even reverse tumor development at various stages in the carcinogenic process. The long latency in tumor development, the multistage nature of the process, and the potential reversibility of some of these stages, offer reasons for optimism that this can be achieved. Advances in our understanding of the fundamental mechanisms by which environmental agents produce disturbances in growth control suggest very specific strategies. This paper provides examples of how recent knowledge in the areas of growth factors, growth factor receptors, protein kinases, signal transduction pathways, oncogenes and growth suppressor genes might lead to the development of such strategies. Major problems will include the development of agents which will specifically act on the target cells of interest without producing toxicity to other tissues, as well as better methods for identifying those individuals who are at risk of developing cancer and, therefore, warrant such therapy.