The development of gene therapy vectors which use selective transcriptional activation of pro-drug systems to target cancer cells requires transcriptional control elements to be cloned from genes known to be expressed at higher levels in tumour cells in comparison to normal cells. Telomerase expression is higher in cancer tissue compared to normal tissue. Thus, we are using telomerase gene promoters for transcriptional targeting of gene therapy vectors. As we move to more clinically relevant models of telomerase-based gene therapy, it is important to determine if the tumour environment influences the telomerase gene promoters.
Tumour hypoxia is the result of inadequate blood supply to the tumour.
Hypoxia inducible promoters can be exploited in cancer therapy to increase tumour specific gene expression. Recently it has been demonstrated that telomerase activity can be induced under hypoxic conditions, however the mechanism for this has not as yet been elucidated. These studies will therefore identify the basic signalling pathways involved in telomerase gene activation during oncogenesis, and its relevance to telomerase-directed gene therapy.