Gap junctions as targets for cancer chemoprevention and chemotherapy

The development of the most efficacious strategy for the prevention and treatment of cancers is based on understanding the underlying mechanistris of carcinogenesis. This includes the knowledge that the carcinogenic process is a multi-step, multi-mechanism process and that no two cancers are alike, in spite of some apparent universal characteristics, such as their inability to have growth control to terminally differentiate, to apoptose abnormally and to have an apparent extended or immortalized life span. The multi-step process, invoking the "initiation" of a single cell via some irreversible process. with the clonal expansion of this initiated cell by suppressing grove fit control and inhibiting apoptosis (promotion step), leads to a situation whereby additional genetic and epigenetic events can take place (progression step) to confer the necessary phenotypes of invasiveness, and metasis (neoplastic stage). While it is clear that in principle, prevention of each of these three steps is possible, in practical terms, while it would make sense to minimize the initiation step, one can never reduce this step to zero. On the other hand, since the promotion step is the rate-limiting step of carcinogenesis, intervening to block this step makes the most sense. Also, by understanding the ultimate biological function that confers growth control, terminal differentiation or apoptosis for cells, there is even some hope of treating some, but not all, malignant cells such that they can regain some ability to perform these vital cellular functions.