New drug trial to target hereditary cancers

Cancer Research UK

Cancer Research UK 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."

For more information on how to take part in the PARP inhibitor BRCA trial visit Cancer Research UK's patient information website CancerHelp UK or call Cancer Research UK's cancer information nurses on 0808 800 4040 (freephone).

Ends

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Notes to Editor

BRCA1 and BRCA2

  • Around 1 in 20 cancers are thought to be caused by high-risk faulty genes inherited from one or both parents.
  • Women carrying the BRCA1 and BRCA2 mutation have a 50-80% chance of developing breast cancer and an increased risk of developing ovarian cancer.
  • In addition to causing breast and ovarian cancer, faults in the BRCA1 or BRCA2 gene can also cause prostate cancer and pancreatic cancer. They may also be involved in other cancers.
  • Genetic testing for faulty BRCA genes is available on the NHS for women with a very strong family history.
  • Intense research into the genetic basis of familial breast cancer led in the 1990s to the identification of the ‘high risk’ breast cancer susceptibility genes BRCA1 and BRCA2.

PARP inhibitor BRCA Trial

  • 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.
  • The trial is investigating whether the new PARP inhibitor drug shrinks tumours in these women.
  • Every woman recruited onto the trial will be treated with the new PARP inhibitor drug. This is not a randomised trial.
  • For more information on how to take part in the PARP inhibitor BRCA trial visit Cancer Research UK’s patient information website www.cancerhelp.org.uk or call Cancer Research UK’s cancer information nurses on 0808 800 4040 (freephone).
  • The PARP inhibitor has already been studied in Phase 1 and 2 clinical trials in Newcastle in combination with another form of chemotherapy.
  • The new trial is building on basic scientific research carried out by Professor Nicola Curtin at Newcastle University, Professor Thomas Helleday from Cambridge University and Professor Alan Ashworth of the Institute of Cancer Research, London.

PARP inhibitors

The development of PARP inhibitors is an exciting area of drug development.

PARP inhibitors block the action of an important enzyme known as PARP [poly (ADP-ribose) polymerase] which is involved in DNA repair.

Although PARP enzymes were discovered over 40 years ago, recent research suggests they could form the basis of new cancer treatments. It also has implications for the treatment of stroke, heart disease and chronic conditions such as arthritis.

Cancer Research UK funded research at Newcastle University.

Cancer Research UK spends over £3 million on a range of research projects at Newcastle University.

Scientists funded by Cancer Research UK at Newcastle University have an international reputation for anti-cancer drug development.

They play a crucial role in delivering the new generation of cancer treatments for children and adults by identifying new drug targets, developing new drugs and verifying the effectiveness and safety of new treatments.

Researchers in medicinal chemistry work in partnership with scientists at the Northern Institute for Cancer Research and doctors and nurses at Newcastle hospitals to help maintain an extensive clinical trials portfolio and ensure that local people have access to the latest cancer treatments.

This collaborative approach means that new treatments can be taken from design in the laboratory right through to evaluation in the clinic, allowing promising new treatments to reach patients quickly.

Cancer Research UK’s Drug Development Office

Cancer Research UK has an impressive record of developing novel treatments for cancer. Since 1982, the Cancer Research UK Drug Development Office has taken over 100 potential new anti-cancer agents into clinical trials in patients, four of which have made it to market, four are in late stage development and many others are in earlier stages of development. These include temozolomide, a drug discovered by Cancer Research UK scientists, that is an effective new treatment for brain cancer. Three drugs are in late development phase III trials and this rate of success is comparable to that of any pharmaceutical company. Further information can be found on the Drug Development Office website.

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