Researchers in the UK have reported promising results from studies of a new type of treatment for cancer that uses an enzyme to direct anticancer drugs to a tumour without causing damage to healthy cells.
The approach, known as gene-directed enzyme prodrug therapy (GDEPT), is being evaluated by a number of scientific groups around the world. In principle it relies on the use of an enzyme – delivered via a gene sequence that is designed only to express the enzyme in malignant cells – that converts a harmless ‘prodrug’ into potent, cancer killing agent.
The aim is that a systemically delivered prodrug will only be activated within cancer cells, leaving healthy cells unscathed. This should reduce side effects and, potentially, allow the dose of anticancer drug that could be delivered to the tumour to be increased.
The Institute of Cancer Research scientists – led by Professor Caroline Springer – have overcome one of the major obstacles to GDEPT, which is getting the prodrugs to cross over the cancer cell membrane and reach the enzyme in sufficient quantities to exert a strong anticancer effect.
The team has developed a series of fluorinated prodrugs, activated by the enzyme carboxypeptidase G2, which delay tumour growth in animal models and human breast cancer cells.
The researchers tested the eight prodrugs on three variants of human breast cancer. Six of the compounds were found to be effective in targeting the affected cell lines, with three being particularly effective in delaying tumour cell growth. The six positive compounds were then tested in animal models. Two compounds resulted in a substantial delay to tumour development, and another two cured two models of their tumours.
Commenting on the study, Prof Springer said: “Although this treatment is more complex than many types of therapies, the fact that it can be so selective in treating cancer means that it is worth exploring further.” At least one of the eight drugs developed by the team is a good candidate for testing GDEPT in clinical trials, she added. Pharmaceutical companies have also got involved in gene-activated product therapy. For example, Innovata and Oxford BioMedica of the UK both have a GDEPT-based treatment in Phase II testing.
