New drug trial to target hereditary cancers

28 Feb 2008

Scientists at Newcastle University are starting the first UK trial of a new drug which targets the ‘Achilles' heel' in hereditary forms of both breast and ovarian cancer.

The trial is open to women who have already developed an advanced form of breast or ovarian cancer and have been diagnosed with faults in the known cancer susceptibility genes BRCA1 or BRCA2.

They will receive a new drug which works by knocking out a key DNA repair mechanism in cancer cells.

It does this by blocking the action of an important enzyme involved in DNA repair, known as PARP [poly (ADP-ribose) polymerase] and is part of a class of potent anti-cancer drugs known as PARP inhibitors.

Cancer Research UK's Dr Ruth Plummer is the chief investigator on the trial.

Dr Plummer, senior lecturer in medical oncology at Newcastle University, said: "People who inherit faults in the BRCA1 or BRCA2 genes have a 50-80 per cent chance of developing cancer."

She continued: "Currently women with hereditary forms of breast and ovarian cancer are treated in the same way as every other woman who develops the disease. We hope this trial will show that by using the PARP inhibitor we can offer them more targeted treatment."

Mutations in the BRCA1 or BRCA2 genes are responsible for around five per cent of the 44,000 cases of breast cancer diagnosed annually in the UK and for more than five percent of the 6,615 cases of ovarian cancer diagnosed each year.

The Newcastle team believe their research could offer hope for the future by paving the way for the drug to be used as a preventative treatment.

Dr Plummer continued: "In the future, we may be able to use the PARP inhibitor to offer protection to women who inherit these genetic faults. We may be able to use it to ‘mop up' stray cancer cells before they actually develop into tumours, thereby sparing the need for preventative surgery."

Throughout our lifetime we accumulate small amounts of damage to our DNA. This can occur naturally as cells work, divide or age.

Normal cells have two DNA strand-break repair mechanisms to patch up this damage or correct mistakes which may occur during replication.

People who inherit faults in the BRCA1 or BRCA2 genes only have one DNA strand-break repair mechanism to help fix damage to their cells. This means they have a higher risk of developing cancer.

But it also means these inherited forms of cancer have an ‘Achilles' heel' and a drug which can disable the only remaining DNA strand-break repair mechanism should also kill the cancer cell.

Professor Herbie Newell, Cancer Research UK's Executive Director of Clinical and Translational Research, said: "The start of this clinical trial is a very exciting development and we look forward to seeing the results." The trial is open in Newcastle and is likely to take 18 months to complete. There are plans to extend it to centres around the UK. Researchers are aiming to recruit 56 women.

Professor Newell added: "The development of 'personalised treatment' tailored to the requirements of an individual patient is becoming a reality and offers the opportunity to design new drugs that are truly selective for different forms of cancer."