On Mother's Day, Dr. Shannon Puhalla will pack her 2-year-old twins into their stroller and walk with them in the 17th annual Susan G. Komen Pittsburgh Race for the Cure to help raise money for cancer research and mammograms for low-income women.

On Monday, she'll be back in the University of Pittsburgh medical laboratories doing her own research of a potential cure for breast, ovarian and pancreatic cancers caused by mutations to the BRCA 1 or 2 genes.

Dr. Puhalla recently enrolled the first of an anticipated 60 patients for a Phase I, National Cancer Institute-funded trial of a biologic cancer-fighting drug called ABT-888. Biologic drugs differ from chemotherapy drugs in that they are targeted, while chemotherapy can kill non-cancerous cells, too.

In previous Phase I trials, ABT-888 has been used in combination and proven to enhance standard chemotherapy's effectiveness. This trial is the first in which ABT-888 will be used as the sole anti-cancer agent.

"Drug companies will come up with their own versions of the same drugs," said Dr. Puhalla, assistant professor of medicine at the university and breast oncologist at Magee-Womens Cancer Program of UPMC Cancer Centers. "In other studies, similar drugs to this one have shown amazing response. ... The response rate has been up above 50 percent in Phase I trials." Typically, drug response rates in Phase 1 trials is 10 percent, she said.

She explained that the BRCA mutations cause cells to use an alternative method of DNA repair that makes errors, which in turn lead to cancer. ABT-888 targets the polymerase, or PARP, family of enzymes responsible for a wide variety of processes in cancer cells. "The class of PARP inhibitors, what they do is block that alternative pathway ... [and] remove any way of cancer cell replicating."

"Someday, BRCA patients may not even need chemotherapy. The drug may work by itself."

If it does, Dr. Puhalla said, "we can translate it into a prevention setting. We can use it to kill off BRCA-mutated cells and obviate the need for [preventative] mastectomies." That, she added, is the "ultimate goal ... to take a pill instead of having a preventative mastectomy."

In the meantime, she said, ABT-888 "definitely can help a lot of people," as the BRCA gene mutation not only can cause breast and ovarian cancer in women, but also prostate and pancreatic cancer and breast cancer in men.

Researchers also speculate that another type of breast cancer caused by an acquired, rather than an inherited, gene mutation called "triple negative breast cancer" would be sensitive to ABT-888. Patients with that type of cancer also will be enrolled in the study. So will women with certain types of chemotherapy-resistant ovarian cancer and people with BRCA-related pancreatic cancer.

Dr. Puhalla estimated the trial will last a year or two.

The ABT-888 trial is just one of "many things we're doing here," she added. "A lot of our focus lately is individualized care -- we sort out what people respond to, what drugs work best, and the term behind that is 'genomics.'

"And the other thing we're looking at a lot is treatments without chemotherapy, more biologically based treatments." Those are called "anti-angiogenic" drugs, and they affect the blood supply to cancerous tumors.

"Chemotherapy is still an important backbone that we use frequently," Dr. Puhalla said, "but we're trying to use drugs that biologically affect tumors instead of chemotherapy, which kills normal cells, too."

For more information about ABT-888 or eligibility for Dr. Puhalla's trial, call 412-641-3494.