NIH study uncovers new mechanism of action for class of chemotherapy drugs
Researchers have uncovered new details on how a class of chemotherapy drugs works.
Balintfy: In recent years, some chemotherapy drugs called PARP inhibitors have been shown to be promising anticancer agents for breast and ovarian cancer.
Pommier: PARP inhibitors have been found to be very promising for patients who suffer from predisposition because of BRCA, breast cancer-associated gene mutations.
Balintfy: Dr. Yves Pommier is with the NIH's National Cancer Institute.
Pommier: So there's a great interest because these patients their tumors was not responsive usually to most therapies and they turn out to be selectively sensitive to these PARP inhibitors. So that's the big interest and there are many drugs in the pipeline today.
Balintfy: PARP, short for poly (ADP-ribose) polymerase, is a protein involved in cell growth. Blocking PARP enzyme activity prevents the repair of DNA damage and ultimately causes cell death.
Pommier: So if you block the poly (ADP-ribose) polymerase, the PARP, then it's much harder for the DNA to be repaired.
Balintfy: Now researchers have discovered a significant new way in which these chemotherapy drugs work. They have also identified differences in the toxic capabilities of some of them. Dr. Pommier explains that these drugs were supposed to just choke the PARP enzyme.
Pommier: In fact, what we found is that some of the drugs do more than that. They poison the enzyme as the enzyme is attaching to the DNA itself and what we revealed is that some of the drugs do these better than others and they poison PARP.
Balintfy: And that he says is what kills the cancer cells. These findings suggest that there may be two classes of PARP inhibitors, ones that mainly inhibit PARP enzyme activity, and others that are dual inhibitors that both block PARP enzyme activity and also trap PARP.
Pommier: PARP inhibitors have to be looked at in this context because their activity is highly dependent on that particular function of trapping PARP on DNA.
Balintfy: Dr. Pommier expects these findings will offer new opportunities to target weaknesses in cancer cells. For more on this study and new cancer research, visit www.cancer.gov. For NIH Radio, this is Joe Balintfy – NIH... Turning Discovery Into Health®.
About This Audio Report
Reporter: Joe Balintfy
Sound Bite: Dr. Yves Pommier
Topic: cancer, chemotherapy, PARP, PARP inhibitors, anticancer, drug