Previously our group was the first to demonstrate by magnetic resonance spectroscopy the possibility of shifting the oxygen disassociation curve and enhancing drug activity in tumours, carried out the first studies of drugs that modulate protein kinases C and A, established the activity of an inhibitor of DNA polymerases d and e in pancreatic and breast cancer and has recently completed the first study of a vascular endothelial growth factor receptor kinase inhibitor. Current trials involve inhibitors of tumour necrosis factor and EGF receptors. In the area of antiangiogenesis, combinations of drugs that inhibit angiogenesis are in phase I, II and III randomised trials. These are also being assessed in combination with chemotherapy. Other drugs inhibiting angiogenesis that are potentiated by hypoxia or inhibiting mitochondrial metabolism in tumours are under study.
Gene therapy using hypoxia promoters to regulate target genes is in trial.
Several pathology studies are planned to apply novel findings in the laboratory to human tumour material particularly relating to DNA repair and angiogenesis. A major commitment is to have pharmacodynamic endpoints to monitor the biological effect of novel drugs in vivo and in tumours. Goals Improve the treatment of cancer by developing new therapies against targets related to our laboratory research, and in collaboration with other ICRF laboratories. Improve our ability to predict survival of patients and their responsiveness to specific therapy by relating pathology studies in the above areas to clinical outcome. Development of gene therapy, DNA vaccination and antiangiogenesis therapy.