PHILADELPHIA A novel therapy designed to attack tumors in patients with a genetic mutation in either BRCA1 or BRCA2, slowed tumor growth in 85 percent of advanced breast cancer patients treated in a small study, researchers report in the July 6 issue of the Lancet.
"That is really an enormous response rate in a population of patients who have received a median of three prior therapies," says study co-author Susan M. Domchek, MD, associate professor of Medicine, University of Pennsylvania School of Medicine, and director of the Cancer Risk Evaluation Program at Penn's Abramson Cancer Center.
"This is the first time that we have been able to take the genetic reason a person has developed cancer and make it a target," Domchek says. "Most of the time we look at what is going on in the tumor itself and then figure out how to target it. But in this situation, the women all had an inherited mutation in either the BRCA1 or BRCA2 gene and we could exploit that weakness in the tumor. It is a strategy that may cause fewer side effects for patients."
The new agent, called olaparib, inhibits a protein called poly(ADP-ribose) polymerase (PARP). Both PARP and the BRCA proteins are involved in DNA repair. And while cells seem to be able to do without one or the other, inhibiting PARP in a tumor that lacks a BRCA gene is too much for the cells, and causes them to die.
"If you put too much stress on the cancer cell, it can't take it and it falls apart," Domchek says. Because the non-tumor cells in a patient with an inherited BRCA mutation still retain one normal copy of the BRCA gene, they are relatively unaffected by PARP inhibition. "These drugs may be very potent in tumor cells and much less toxic in normal cells. That is important from the perspective of cancer treatment," Domchek says.
The international study enrolled 54 patients in two groups. The first group of 27 women received 400 mg oral olaparib twice daily and th
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University of Pennsylvania School of Medicine