Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4.

There are still many unanswered questions regarding the processes by which extracellular signals are transduced from plasma-membrane receptors to the transcription machinery in the nucleus and the translation machinery in the cytoplasm. Some of these gene expression events become misregulated as a result of environmental or endogenous exposure to agents that cause multistage carcinogenesis. We are now beginning to identify and validate the crucial molecular events that drive the rate-limiting steps of carcinogenesis and to target these events for cancer prevention. Transcription factors AP-1 and nuclear factor kappa B can be specifically targeted to prevent cancer induction in mouse models. A protein known as programmed-cell-death-4 is a new potential molecular target that has a surprising mode of action.