Transcriptional control: An essential component of cancer gene therapy strategies?

The therapeutic index of cancer gene therapy approaches will, at least in p art, be dictated by the spatial and temporal control of expression of the t herapeutic transgenes. Strategies which allow precise control of gene trans cription are likely to play a crucial role in the future pre-clinical and c linical development of gene therapy. In this review, we discuss these issue s as they relate to tissue and tumor specific promoters. In addition, the e xciting opportunities offered by the development of regulated gene expressi on systems using small molecules, radiation and heat are reviewed. It is re alistic to expect that the future offers the prospect of amalgamating eleme nts of a number of these different systems in a co-ordinated gene delivery approach with the potential to increase the efficacy and reduce the toxicit y of treatment. (C) 2000 Elsevier Science B.V. All rights reserved.