A Potential Approach to Gene Therapy of Cancer
Enormous progress has recently been made in the characterization of the biochemical and molecular events associated with the control of the mammalian cell cycle and with cell replication. Some of the normal cellular genes engaged in such regulatory functions have been shown to lead to, or be associated with, aberrant growth of cells and to the development of the neoplastic changes in the cells. There are at least two kinds of genes associated with the aberrant growth properties of tumor cells (Bishop 1991). Mutated, activated forms of the normal cellular proto-oncogenes are able to cause neoplastic transformation of cells by disrupting the normal controlled mechanisms of cell replication and growth. Their gene products can be imagined to provide positive stimuli to cellular growth. The presence of a single mutated allele is sufficient to cause cell transformation, and the continued presence and expression of the other, wild- type allele is insufficient for the maintenance of the normal cellular phenotype (Fig. 1). Potential therapeutic approaches toward the genetic reversal of these kinds of defects might include interference with translation of oncogene messenger RNAs by the introduction of anti-sense sequences or ribozymes specific for the oncogene transcript, the introduction of transdominant wild-type alleles or the introduction of non-allelic genes encoding functions that interfere with the transforming function of the oncogene (Fig. 2).
KeywordsTumor Suppressor Gene Familial Cancer Syndrome Normal Cellular Growth Growth Suppress Function Normal Control Mechanism
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