New Class of Drugs Promising for BRCA-Related Cancers
Article date: June 30, 2009
By Rebecca V. Snowden
New drugs called PARP inhibitors appear to have a lot of promise against hereditary cancers caused by BRCA1 and BRCA2 cell mutations.
PARP inhibitors work by blocking the action of poly (ADP-ribose) polymerase, an enzyme that helps repair DNA. In certain tumor cells, such as those from BRCA1 and BRCA2 mutation carriers, blocking this enzyme can lead to cell death.
People who carry BRCA1 and BRCA2 mutations are at a higher risk of developing many cancers, including breast, ovarian, and prostate cancers. Scientists hope PARP drugs can be used to effectively target the cancer cells in those people without destroying their healthy cells, minimizing harsh side effects.
In a small phase I study, researchers at the Institute of Cancer Research in Sutton, England tested the action of a PARP drug called olaparib in 60 patients, 22 of whom were known carriers of the BRCA1 or BRCA2 mutation, and 1 who likely was a carrier. The patients started with a dose of 10 mg of the drug orally once daily, for 2 of every 3 weeks, then the dose and length of treatment were gradually increased to find the best way of giving the drug.
The study group included 20 men and 40 women with different types of cancer -- ovarian, breast, colorectal, prostate, melanoma, as well as some other types. About half had had more than 4 previous cancer treatments.
Twelve patients with inherited BRCA1 or BRCA2 mutations saw their tumors shrink or stop growing. These patients all had ovarian, breast, or prostate cancer. The drug had no effect on patients who were not BRCA1 or BRCA2 carriers.
Side effects were minimal compared to traditional chemotherapy drugs and included nausea (32%), fatigue (30%), and vomiting (20%).
The findings are so promising they were published recently in The New England Journal of Medicine, which typically doesn't publish results from early phase I studies. An accompanying editorial calls the drugs "a new direction in cancer-drug development."
And PARP drugs appear to be effective against other cancers, as well.
Another study, which was presented recently at the Annual Meeting of American Society of Clinical Oncology, found that the PARP drug BSI-201 improved survival in women with triple-negative breast cancer compared to traditional chemo. Because triple-negative breast cancer lacks certain receptors, it doesn't respond to hormone therapy or drugs that target HER2, such as Herceptin.
However, while these findings are very encouraging, PARP drugs are still in the early stages of development and more testing is needed.
Citation: "Inhibition of Poly(ADP-Ribose) Polymerase in Tumors From BRCA Mutation Carriers." Published June 26, 2009 in The New England Journal of Medicine. First author: Peter C. Fong, MD.
"Synthetic Lethality – A New Direction in Cancer-Drug Development." Published June 26, 2009 in The New England Journal of Medicine. J. Dirk Inglehart, MD and Daniel P. Silver, MD, PhD.
Reviewed by: Members of the ACS Medical Content Staff
ACS News Center stories are provided as a source of cancer-related news and are not intended to be used as press releases.
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