Molecular targeting of gene therapy and radiotherapy

The full promise of gene therapy has been limited by the lack of specificit y of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. In this paper we review our st udies investigating two modifications of gene therapy combined with radioth erapy. The first investigations described include studies of radiation indu cible gene therapy. In this paradigm, radio-inducible DNA sequences from th e CarG elements of the Egr-1 promoter are cloned upstream of a cDNA encodin g TNF alpha. The therapeutic gene (TNF alpha) is induced by radiation withi n the tumor microenvironment. In the second paradigm, genetically engineere d herpes simplex virus (HSV-1) is induced by ionizing radiation to prolifer ate within the tumor volume. These modifications of radiotherapy and gene t herapy may enhance the efficacy of both treatments.