Breast
PARP Inhibitors- A Breakthrough in Breast Cancer Treatment
By KuDOS Pharmaceuticals, Cambridge, Uk
Apr 15, 2005, 18:18

According to new research published in Nature today (14 April 2005), UK scientists have identified a potential new drug which could dramatically improve the treatment of patients with certain types of hereditary breast cancer and herald a new approach to targeted cancer therapy.

Women carrying faults in the BRCA1 and 2 genes have up to an 85% chance of developing breast cancer by the age of 70. Currently there is no specific treatment available for these women.

Now, scientists � funded by Breakthrough Breast Cancer and Cancer Research UK � at the Breakthrough Toby Robins Breast Cancer Research Centre (London) in collaboration with KuDOS Pharmaceuticals (Cambridge), report that a new drug, known as a PARP* inhibitor, may be very effective in killing tumour cells in people who have faults in BRCA1 and BRCA2. The drug is likely to be much less toxic to healthy cells than standard chemotherapy.

Professor Alan Ashworth, Director of the Breakthrough Research Centre � situated at The Institute of Cancer Research � who led the research in London, said: �This is a brand new therapeutic approach, centred on exploiting a specific deficiency in breast cancer cells � their Achilles� heel. This is only possible because of our ever-increasing understanding of the basic molecular biology of cancer.� Professor Ashworth was instrumental in the discovery of the BRCA2 gene in 1995.

In the UK, nearly 41,000 women are diagnosed with breast cancer each year. Of these, 5% are due to strong hereditary factors, some of which are caused by BRCA1 and BRCA2 mutations.

Most breast cancer patients are treated with drugs that kill tumour cells but also damage normal cells. It is damage to normal cells that can lead to distressing side effects, like nausea and hair loss. The advantage of this new approach is that it is targeted; tumour cells are killed while normal cells appear unaffected. This is because the new class of drugs, PARP inhibitors � being developed by KuDOS Pharmaceuticals � exploit the specific genetic make-up of some tumour cells.

Breast tumours in women who inherit faults in either the BRCA1 or BRCA2 genes occur because the tumour cells have lost a specific mechanism that repairs damaged DNA**. PARP inhibitors selectively kill cells where this form of DNA repair is absent and so are highly effective in killing BRCA deficient tumour cells and other similar tumour cells. Normal cells are largely unaffected by the drug as they still possess this crucial DNA repair mechanism.

Dr Andrew Tutt, a Clinician Scientist at the Breakthrough Research Centre and Breast Oncologist at Guy�s Hospital, said: �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.�

KuDOS, a leading privately owned oncology company, has been developing the PARP inhibitor programme since 2000. Professor Steve Jackson, Chief Scientific Officer of KuDOS, who founded KuDOS in1997, commented: "This is the first time that a PARP inhibitor has shown significant promise as a treatment for breast cancer. This discovery could well be the tip of the iceberg, as the DNA repair technology behind this programme has the potential to treat a range of other cancers that display similar characteristics."

Dr Lesley Walker, Director of Cancer Information at Cancer Research UK, said: "Collaborations like this, that bring together all the necessary expertise, are crucial for the rapid and effective translation of fundamental research into a new generation of smart cancer treatments."

The PARP inhibitors will enter Phase I trials within a few months, to monitor the safety of the drug and determine the most effective dose to take into larger clinical trials. If these trials are successful, these drugs will be ready for testing in clinical trials of patients with BRCA deficient tumours.

This new treatment might also be applicable to other forms of breast cancer that behave like BRCA deficient cancer. This group may represent more than 20% of all breast cancers and is a key area of research in Professor Ashworth�s laboratory.

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