GENETIC RADIOTHERAPY

Recent studies have shown that experimental turners could be treated m ore efficiently with ionizing radiation if genetic material was transf ered into tumor cells. Several approaches have been reported, and amon g them, the first one consisted of increasing the apoptotic response t o radiation by modulating genes involved in the regulation of the apop totic pathway. Indeed the modulation of p53 and bcl-2 gene expression has recently been used successfully in several experimental models to increase the apoptotic death after radiation. A second approach consis ted of taking advantage of the conditional expression of some genes af ter exposure to ionizing radiation. Indeed, some genes exhibit a radio -inducible promotor which can be combined to a gene, able to enhance o r decrease the biological effect of radiation. The irradiation of such a transgene under the control of a radio-inducible promotor can lend to a second biological effect, concomitant to the irradiation, as repo rted for the TNF alpha under the control of the EGR (early growth resp onse) promotor. A third approach consisted of enhancing the effect of radiation induced tumor cell death by the expression of a suicide gene in these cells, as suggested recently for the HSV-tk (herpes virus th ymidine kinase gene). These preliminary results obtained in experiment al models appear to be very promising and might improve the efficacy a nd specificity of radiation therapy in a not too distant future.