Apoptosis: a novel therapeutic tool?
Apoptosis is a genetically programmed cell death mechanism that appears to occur in all multicellular organisms. It is a normal process that serves to maintain cellular homeostasis. However, in many diseases there is a disruption in the equilibrium between cell proliferation and cell death that contributes directly to the disease. In these cases, a possible therapeutic intervention would be to restore the skewed equilibrium by pushing it in the desired direction through the use of pharmacological agents or genetic approaches. These observations have instigated substantial research in the field of apoptosis, resulting in an increasingly detailed analysis of the molecular mechanisms and the sequence of events that occur in this cell death pathway. In addition, by trying to understand this pathway, several potential therapeutic agents have arisen from those used in chemo-, radio-, and cytokine therapy. While these agents have been relatively successful, it is rare that their effect is complete. Thus, the search continues for a strategy to conquer those cells that are resistant to these regimens. Genetic approaches are novel and have been shown to be quite successful in several in vitro and animal models. They also tend to have low toxicity. It is believed that using a more traditional front-line approach of therapy, supplemented by appropriate genetic intervention, will allow substantial increases in the efficacy of treatment, while at the same time introducing little or no additional toxicity.
Medicine Branch, Clinical Pharmacokinetics Unit, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. nemra@box-n.nih.gov
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