Five to ten percent of all breast, ovarian and prostate cancers can be attributed to mutations of the BRCA1 and BRCA2 genes. Now, for the first time, researchers have shown that a new class of drugs called PARP inhibitors may be effective in treating the diseases. In a small study, researchers from the Institute of Cancer Research gave 19 patients with inherited forms of advanced breast, ovarian and prostate cancers a PARP inhibitor called Olaparib. In 12 of those patients, none of whom had responded to any other type of treatment, their tumors either shrank or became stabilized. In addition, patients experienced very few side effects.

PARP inhibitors work by targeting cancer cells, leaving healthy cells relatively untouched. Olaparib is the first drug to successfully use a technique called "synthetic lethality," which exploits the body's own molecular weaknesses. While normal cells utilize a variety of pathways to repair damage to their DNA, in tumor cells, one of those pathways is disabled by the BRCA mutation. Olaparib does its job by shutting down an enzyme called PARP, thereby blocking one of the repair pathways. Since the DNA in those cells that have defective genes cannot be repaired, the tumor cells die. Normal cells are not affected since they can enlist the help of an alternative repair mechanism controlled by their healthy BRCA genes.

A member of the research team, Dr. Johann de Bono, says that the drug should now be tested in larger trials. "This drug showed very impressive results in shrinking patients' tumors. It's giving patients who have already tried many conventional treatments long periods of remission, free from the symptoms of cancer or major side-effects," he says. And in fact, one of the first patients to undergo the treatment is still in remission after two years.

While the drugs have worked only in people with BRCA 1 and BRCA2 mutations resulting in breast, ovarian and prostate cancers, there is evidence they may be effective in other cancers with different defects in the repair of DNA. As Professor Stan Kaye, who also worked on the study, notes: "The next step is to test this drug on other more common types of ovarian and breast cancers where we hope it will be just as effective."

News Release: New cancer drug shows promise www.bbc.co.uk June 24, 2009