New breast cancer drugs block cell repair enzyme

May 31, 2009

New breast cancer drugs block cell repair enzyme

Sun May 31, 2009 3:41pm EDT

By Deena Beasley

ORLANDO, Florida (Reuters) – Drugs that block a cell repair enzyme known as PARP show promise as treatments for some of the most aggressive and difficult-to-treat forms of breast cancer, according to new research.

Mid-stage results from a PARP inhibitor developed by BiPar Sciences Inc show that it improved survival by 60 percent compared with chemotherapy alone for women with “triple negative breast cancer.”

And a small trial of AstraZeneca Plc’s olaparib as a stand-alone therapy in women with advanced breast cancer linked to genetic mutations showed that it shrank tumors in a third of patients.

“While still very preliminary, these are some of the most exciting results we have seen in a long time,” said Dr. Eric Winer, breast cancer chief at Boston’s Dana-Farber Cancer Center.

The findings were presented on Sunday at the annual meeting of the American Society of Clinical Oncology.

PARP is short for “poly (ADP-ribose) polymerase,” which is used by cancer cells to repair DNA damage, including the damage inflicted by chemotherapy drugs. By blocking the enzyme, researchers aim to further undermine the ability of cancer cells to heal themselves.

Breast cancer was one of first types of cancer that scientists have been able to divide into subgroups based on biological markers.

Back in the 1970s they identified women whose tumors contained estrogen receptors — paving the way for the development of hormonal therapies, like tamoxifen and aromatase inhibitors.

That breakthrough was followed by the launch in 1998 of Herceptin, an antibody-based drug designed to target the HER-2 protein, which is generated by around 25 percent of breast cancer patients.


“The third breakthrough is this one,” said Dr. Barry Sherman, head of development at BiPar, which presented results from a 116-patient trial of its intravenous PARP inhibitor, known as BSI-201.

Privately held BiPar agreed in April to be purchased by French drugmaker Sanofi Aventis SA for up to $500 million.

BSI-201 is being studied in women with “triple negative” metastatic breast cancer, meaning their tumors do not express the hormones estrogen or progesterone as well as HER-2.

These women, accounting for 15 to 20 percent of breast cancer patients, have a very aggressive form of the disease and there are currently no treatments beyond chemotherapy, Sherman said.

The BiPar trial found women who received BSI-201 had a median survival of 9.2 months, compared with 5.7 months for the chemotherapy-only group. Tumors shrank in nearly half of patients treated with the BiPar drug, compared with just 16 percent of patients on chemotherapy alone.


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