Cancer sufferers to be drug trial guinea pigs

Feb 28 2008 by Audrey Barton, The Journal

TWO North East women with advanced cancer are the first in the country to act as guinea pigs for a new drug developed in the region to treat hereditary tumours.

Cancer Research UK scientists at Newcastle University have started the first clinical trials to treat women with advanced-stage breast and ovarian cancer caused by a faulty gene.

Another five women are being screened for their suitability to take part in the trial and more are being sought to see if the targeted drug developed in Newcastle shrinks their tumours.

Scientists at the Northern Institute for Cancer Research, the first centre in the country to trial the drug, believe it could treat thousands of women diagnosed with a hereditary form of two of the most common types of cancer each year. The revolutionary treatment developed after 18 years of research at the institute is the first of its kind to target the ‘Achilles heel’ of inherited cancer.

Currently women who have lost relatives to the disease face a dilemma of whether to be tested for the faulty gene, which greatly increases their risk of getting cancer. But the new drug could take away their fear of the future as it may go one step further in protecting women at risk from developing the cancer at all.

Professor Hilary Calvert, director of the Northern Institute for Cancer Research, said: “This is a very exciting moment for me as it’s a culmination of many years of developing new drugs in Newcastle, something we have done here with a great deal of support from Cancer Research UK.

“We have come up with a drug which is quite remarkable and the first of its type to be given to people with cancer. It is more selective than chemotherapy and has less side effects.” Mutations in the BRCA1 or BRCA2 genes are responsible for around 5% of the 44,000 cases of breast cancer diagnosed annually in the UK and for more than 5% of the 6,615 cases of ovarian cancer diagnosed each year.

In the North-East, 2,000 women are diagnosed with breast cancer each year, 280 with ovarian cancer.

Although relatively rare, those carrying the faulty gene have up to an 80% chance of developing breast cancer and an increased chance of ovarian.

Researchers at Newcastle University’s Institute of Human Genetics invented a new method of testing for the gene last year. Women with a strong family history are currently screened for the gene on the NHS and that is expected to be expanded to more people, using the Newcastle method.

Now clinical trials have begun in Newcastle to test the drug which works by knocking out a key DNA repair mechanism in the cancer cells on women who have tested positive for the gene. The drug is from a class of potent anti-cancer drugs known as PARP inhibitors and scientists hope that if it proves to be successful, it will be available to treat patients with these hereditary diseases within three to four years.

Dr Ruth Plummer, senior lecturer in medical oncology at Newcastle University, said: “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.”

The drug could be used before traditional treatment chemotherapy as it is more selective and has so far shown very few side effects.

Scientists also believe it could be used to target thousands more patients with hereditary pancreatic and prostate cancer which can also be linked to these particular faulty genes.

Eventually researchers hope the drug could be used to protect women by preventing cancerous cells becoming tumours.

Dr Plummer added: “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.”

Professor Herbie Newell, Cancer Research UK’s executive director of clinical and translational research, said: “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.”

The Genes

AROUND one in 20 cancers are thought to be caused by high-risk faulty genes inherited from one or both parents.

Normal cells have two DNA strand-break repair mechanisms to patch up damage to DNA.

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, which 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.

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.

The 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.

It is investigating whether the new PARP inhibitor drug shrinks tumours in these women.

Every woman recruited on to 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 Drug

THE development of this particular type of PARP inhibitor marks the end of 18 years of research by the Northern Institute for Cancer research.

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

PARP inhibitors block the action of an important enzyme 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.