London: Scientists have developed a new therapy which they claim could significantly slow tumour growth in patients with advanced breast cancer. An international study has found that the therapy, designed to attack tumours in patients with a genetic mutation in either BRCA1 or BRCA2, slowed tumour growth in 85 per cent of advanced breast cancer patients, `Lancet` journal reported. "That is really an enormous response rate in a population of patients who have received a median of three prior therapies. 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. "Most of the time we look at what is going on in the tumour itself and then figure out how to target it. But in this situation, the women all had an inherited mutation ineither the BRCA1 or BRCA2 gene and we could exploit that weakness in the tumour."It is a strategy that may cause fewer side effects for patients," said lead author Susan M Domchek of University of Pennsylvania. 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 tumour 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. These drugs may be very potent in tumour cells and much less toxic in normal cells. That is important from the perspective of cancer treatment," Domchek said. In fact, the study enrolled 54 patients in two groups. The first group of 27 women received 400 mg oral olaparib twice daily and the second group of 27 patients received 100 mg oral olaparib twice daily. The higher dose appeared to have more activity against the disease, with one patient having a complete resolution of her tumour and 10 showing substantial tumour shrinkage.Another 12 women had stable disease or some tumour shrinkage, but not enough by standard norms. In the low dose group, six patients showed substantial shrinkage and 12 had some tumour shrinkage or stable disease. Although the results look good thus far, Domchek said that more clinical trials will be necessary before olaparib or other PARP inhibitors in development will be ready for use in regular practice.
"In oncology, this is really one of the first times that we`ve seen drugs being developed on the basis of inherited susceptibility -- and that may open up a whole new avenue of drug development," Domchek said. Bureau Report
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