New class of drugs for hereditary breast cancer enters clinical trials
Breast cancer cells with mutations in BRCA genes would be target |
A potential new class of drugs, poly(ADP-ribose) polymerase (PARP) inhibitors, to treat women with hereditary breast cancer has shown promising results in animal studies and is about to enter phase I clinical trials.
Two research groups in the UK, one at the Institute of Cancer Research,
London, and one at Sheffield University, have discovered this novel,
targeted approach to the treatment of breast cancers caused by mutations
in BRCA1 and BRCA2 genes. Both groups published their work in Nature last month (2005;434:913 and 917).
Before cell replication, DNA damage is repaired by an enzyme called PARP.
If this enzyme is absent then cells use an alternative mechanism, called
homologous recombination, to repair the damage and continue to replicate.
BRCA1 and BRCA2 are necessary for homologous recombination and so PARP
becomes essential in cells that have BRCA1 and BRCA2 mutations.
The research groups propose that if PARP is blocked, DNA lesions — that
would normally be repaired by homologous recombination — will persist and
that this leads to cell death. They argue that PARP inhibitors are highly effective
at killing BRCA-deficient tumour cells leaving normal cells largely unaffected,
thereby potentially reducing side effects such as hair loss and nausea.
The groups have validated this therapeutic approach by showing that PARP inhibitors
slow the growth of BRCA2 deficient tumours in mice. Andrew Tutt, a clinical scientist
at the Breakthrough Research Centre at the Institute of Cancer Research, commented: “Targeted
treatment holds considerable clinical promise. If our laboratory findings are
confirmed in the clinic, we could dramatically improve the treatment of patients
with BRCA1 or BRCA2 associated cancers. This is a completely new approach in
our fight against this type of cancer.” |
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