Researchers at Stockholm University have, together with colleagues in England, discovered a new way of treating and preventing hereditary breast cancer. The article, published in Nature, describes how the use of a chemical inhibitor can specifically kill tumour cells, which have a defect in the gene causing hereditary breast cancer. This new treatment targets only the tumour cells and is not likely to affect other healthy cells in the body. The discovery could also lead to a prophylactic treatment for hereditary breast cancer.

In most women, the BRCA1 and BRCA2 genes prevent breast tumours from forming, but some women have inherited mutations in these genes, giving them about an eighty per cent risk of developing breast cancer.

Normal cells replicate by dividing DNA into two strands and copying each strand. Before replication, damage in the DNA is usually repaired using a protein called PARP. If PARP is absent or inhibited then the cells use a second mechanism called recombination to fix the damage and continue to replicate. Cells with mutated BRCA genes can't undergo recombination and therefore rely completely on PARP to fix the damage.

The new treatment uses a chemical that prevents PARP from repairing the DNA, making recombination essential. The breast cancer tumour cannot perform recombination and is therefore unable to replicate and create new cells. The tumour is then unable to grow and eventually dies.

The beauty of this system is that only the tumour cells lack BRCA genes and thus only they completely rely on PARP. The other cells in the body are likely to be unaffected by the treatment and continue to use recombination to repair any mistakes that occur."

-- Since normal cells don't need the PARP backup system to survive we could use PARP inhibitors as a prophylactic treatment to kill BRCA deficient cells before they grow out to tumours, says Dr Thomas Helleday, associate professor at Stockholm University who
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Contact: Agneta Paulsson
agneta.paulsson@eks.su.se
46-08-16-2256
Swedish Research Council
14-Apr-2005

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