The drug, called olaparib, specifically targets hereditary cancer caused by faulty BRCA1 and BRCA2 genes. The small scale patient trial has shown remarkable benefit for patients with breast, ovarian and prostate cancer.

The trial was carried out by The Institute of Cancer Research with the Royal Marsden Hospital, working with pharmaceutical company AstraZeneca, with results published in the New England Journal of Medicine on 9 July 2009.

The journal's editorial said: "This trial not only reports important results - it also points to a new direction in the development of anticancer drugs."

The results of the Phase I trial showed that, despite having had many standard therapies prior to taking olaparib, more than half of patients' tumours shrank or stabilised. One of the first patients to be treated is still in remission after two years. Phase I trials look at dosage levels, side effects and if the drug shrinks tumours.

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre, said: "We are delighted that the work we did in the lab has been translated so quickly into benefit for patients. We are hopeful that olaparib could provide a new targeted treatment for women with BRCA-related breast cancer. However, this drug is still at an early stage of development and further clinical trials are necessary to fully evaluate its potential."

The initial research into a potential targeted treatment for BRCA-related breast cancers was carried out by Professor Ashworth's team at the Breakthrough Research Centre in London, working with KuDOS pharmaceuticals, now part of AstraZeneca . It is through this research that the discovery of a very specific weakness of these tumours was made. This research enabled the further investigation of olaparib in a clinical trial.

Through an rational new approach, called synthetic lethality, olaparib kills cancer cells with a faulty BRCA1 or BRCA2 gene by preventing the repair of DNA. A cell with a BRCA fault relies on a protein called PARP to keep its DNA healthy. Olaparib, known as a 'PARP-inhibitor', blocks PARP, which causes the cancer cells to die. This means that the tumour should either stop growing or get smaller. Due to the drug working in a targeted way, it kills cancer cells while leaving healthy cells relatively unaffected, which means fewer side effects for patients.

A Phase II clinical trial is ongoing and being carried out by Dr Andrew Tutt, Director of the Breakthrough Breast Cancer King's College London research unit at Guy's Hospital. He presented early results at the American Society of Clinical Oncology conference in Florida, USA, in May 2009.

The trial looks at dose levels, side effects and how well the treatment works. It studies a group of 54 women with advanced breast cancer who have already received chemotherapy. In the initial findings, 27 patients took 100 mg doses of olaparib with another 27 who took 400 mg doses. Over 40% of tumours in the higher dose group reduced significantly in size, and tumours were prevented from progressing for an average of six months, while one patient's tumour disappeared completely. Most patients had only relatively minor side effects, such as fatigue and nausea.

Jeremy Hughes, Chief Executive of Breakthrough Breast Cancer, said: "Targeted drugs are a key part of the future of cancer treatment and we are pleased to see the first clinical trial results of a drug for women with breast cancer due to faulty BRCA 1 and BRCA2 genes. It is very encouraging to see the potential impact of the research Breakthrough has invested in, and the hard work of our scientists in improving treatment for patients."

Breakthrough Breast Cancer scientists think that if future trials are positive, olaparib could offer hope to patients with certain types of breast and ovarian cancers that are currently hard to treat. Scientists are already suggesting that it could be used for other forms of cancer with similar characteristics and open the door to a new generation of cancer treatments using the same approach.

Breakthrough Breast Cancer relies on voluntary donations to tackle the disease through research, campaigning and education and needs to raise at least £19 million a year to support this vital work across the UK.

For more information about Breakthrough Breast Cancer and how to support its work, please visit http://www.breakthrough.org.uk or call 08080 100 200.

Notes

Olaparib clinical trials

The New England Journal of Medicine article reports on the results of a Phase I study involving BRCA1/2 mutation carriers with several cancer types. Recruitment for a Phase II trial has been completed and the trial is ongoing. The drug is also being tested in other groups of non-breast cancer patients, and some trials may still be recruiting, although all will have strict eligibility criteria. For details, check http://www.cancerhelp.org.ukor http://www.clinicaltrials.gov.

About hereditary breast cancer

In about 5% of the nearly 46,000 cases diagnosed in the UK each year, breast cancer is caused by an inherited fault in the BRCA1 or BRCA2 gene. Around 5-10% of cases are thought to be due to a family history of breast cancer. A family history of breast cancer is identified as an unusually high number of close relatives with breast or other types of cancer, breast cancers at a young age, or breast cancers in men as well as women.

Breast Cancer

- Breast cancer is the most commonly diagnosed cancer in the UK - nearly 46,000 women and around 300 men are diagnosed every year.
- Breast cancer accounts for nearly 1 in 3 of all female cancers and one in nine women in the UK will develop breast cancer at some point in their lifetime.
- The good news is that more women than ever in the UK are surviving breast cancer thanks to better awareness, better treatments and better screening.

Professor Alan Ashworth, FRS, Director of the Breakthrough Research Centre

Professor Alan Ashworth studied for his BSc in Chemistry and Biochemistry at Imperial College, London before completing his PhD in Biochemistry at University College, London. Since 1986, he has worked in the Chester Beatty Laboratories at The Institute of Cancer Research (ICR) in London and was a member of the team that discovered the BRCA2 gene in 1995.

In 1997, Alan was appointed Professor of Molecular Biology and became Head of Section of Gene Function and Regulation at the ICR. He was appointed Director of the Breakthrough Breast Cancer Research Centre on 1 August 1999. He is an elected member of EMBO and the Academy of Medical Sciences. In May 2008, Professor Ashworth was elected as a fellow of the Royal Society for his major contributions to mammalian genetics, and the identification and study of inherited cancer susceptibility genes.

Breakthrough Breast Cancer

Breakthrough Breast Cancer is the UK's leading charity committed to fighting breast cancer through research, campaigning and education. In 1999 Breakthrough established the UK's first dedicated breast cancer research centre. The Breakthrough Toby Robins Breast Cancer Research Centre is housed in the Mary-Jean Mitchell Green building at The Institute of Cancer Research in association with the Royal Marsden Hospital.

Under the directorship of Professor Alan Ashworth FRS, the Breakthrough Research Centre now has 120 world-class scientists and clinicians tackling breast cancer from all angles - from understanding the normal growth and development of the breast, how breast cancer arises and how the cancer spreads, to treatment and ultimately disease prevention. Scientists at the Breakthrough Research Centre, funded almost entirely from voluntary contributions, have a range of expertise and approaches and together they are working towards a common goal: a future free from the fear of breast cancer.

Breakthrough has opened research units in Edinburgh and London with a third to open in Manchester in 2009.

Source
Breakthrough Breast Cancer