Gene therapy in the treatment of human cancer

Abstract

Cancer can be considered a disease caused by mutations and/or epigenetic changes in tumor suppressor genes and oncogenes that populate the host genome. It is well established that most of the genetic events in cancer result from a series of accumulated, acquired genetic lesions. These genetic events either inactivate tumor suppressor genes or activate oncogenes. With an enhanced understanding of the genetic lesions associated with malignant transformation and progression in a wide variety of human cancers, different therapeutic approaches are being identified. In this regard, gene therapy is emerging as a method of preventive and therapeutic intervention against cancer targeted at the level of cellular gene expression. In this approach, altering the complex cancerous pathophysiologic state is achieved by delivering nucleic acids into cells. These nucleic acids may be genes, portions of genes, oligonucleotides, or RNA. In conventional therapeutics, as in pharmacotherapy, altering a cell or tissue phenotype is accomplished by altering cell physiology or metabolism at the level of protein expression. In contrast, in gene therapy this is accomplished by changing the pattern of expression of genes whose products may correct defects in cellular phenotype.