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Hope for new drug to treat inherited breast, ovarian and prostate cancers

29 June 2009
Appeared in BioNews 514

A new drug for the treatment of inherited forms of breast, ovarian and prostate cancer has shown promising results in early clinical trials. The study, published in the New England Journal of Medicine, reported that the drug promoted tumour reduction and clinical improvement in advanced-stage cancer patients whilst causing fewer side effects than conventional chemotherapy.

The new drug, Olaparib, made by AstraZeneca, was given to 60 adult patients with advanced cancers that had returned after previous treatment and for which no current alternative treatments were available. As a phase I clinical trial, the purpose was primarily to investigate the safety of the drug and the side effects it caused, rather than as a rigorous test of its efficacy. The trial was run by the Institute of Cancer Research, London, UK, and selected patients from various institutes across the UK and the Netherlands. The drug was administered in increasing doses over a period of several weeks, provided that no serious side effects were observed. The results showed that it was safe and had fewer adverse effects than other current forms of chemotherapy.

Out of the 60 patients in the trial, 21 had breast, ovarian and prostate cancers associated with inheriting dysfunctional BRCA1 or BRCA2 gene variants. The presence of these gene variants was confirmed by DNA testing in 20 of these patients and strongly suspected in the remaining one due to family history. Two of these patients were not able to be evaluated at the end of the trial, but of the remaining 19, 12 showed clinical improvements. Dr Johann de Bono, who led the study, said: 'this drug showed very impressive results in shrinking patients' tumours. It's giving patients who have already tried many conventional treatments long periods of remission, free from symptoms of cancer or major side-effects'. No improvements were seen in the 39 patients who did not have BRCA1- or BRCA2-associated cancers.

Olaparib works by triggering the death of cancer cells without affecting healthy cells, thus reducing the number of side-effects compared to other anti-cancer drugs. It is a new type of drug called a PARP inhibitor, as it blocks the activity of an enzyme called PARP that acts to repair damaged DNA. DNA damage occurs all the time in our body and cells have several mechanisms to repair this damage in order to prevent the accumulation of harmful mutations. In normal cells, blocking PARP has no effect as a second DNA repair pathway controlled by the genes BRCA1 and BRCA2 prevents mutations. However, in cancer cells in which BRCA1 or BRCA2 is dysfunctional, blocking PARP causes cell death as the cells rapidly develop too many mutations to be viable.

Larger clinical trials are now planned that are hoped to confirm the efficacy of Olaparib in treating BRCA1- and BRCA2-associated cancers, as well as other cancers caused by different defects in DNA repair mechanisms.

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