I’m a Cancer Patient. Should I Ask About PARP Inhibitors?

Ask your doctor to see if you are eligible for any of the current trials for PARP inhibitors.

Deborah Armstrong, M.D.

PARP stands for poly ADP-ribose polymerase, an enzyme found in the nucleus of cells that is responsible for repairing damage to DNA. While repairing DNA is critical to preventing the genetic mutations that give rise to cancer, many treatments for cancer actually aim to damage the DNA of the cancer cell. Many chemotherapy drugs used today directly or indirectly work by damaging DNA and do this more potently in cancer cells than in normal cells.

PARP inhibitors work by inactivating the PARP enzyme. There are at least eight PARP inhibitors in development, but none are yet approved by the Food and Drug Administration. PARP inhibitors have been of particular interest for patients who have a cancer that is associated with a BRCA mutation, such as those with familial breast or ovarian cancer. The BRCA proteins, important in one DNA repair pathway, are inactive in these BRCA-associated cancers. When a second DNA repair pathway is inactivated using a PARP inhibitor, BRCA-associated cancers show response rates that are significant and sometimes higher than would be expected with other available treatments.

In other studies, PARP inhibitors are used with chemotherapy agents whose toxicity is repaired by PARP in the cancer cell. Inhibiting PARP makes the cancer cell more susceptible to the chemotherapy. One of these is the drug temozolomide, used to treat certain brain tumors and melanoma. Other studies have used PARP inhibitors in combination with platinum agents, chemotherapy drugs used to treat a wide variety of cancers, such as ovarian, lung, and testicular cancers, among others. One highly publicized study showed a significant increase in the response of patients with "triple negative" breast cancer when chemotherapy was given with a PARP inhibitor. In triple-negative breast cancer, three treatment targets—the estrogen receptor, the progesterone receptor, and HER2/neu—are all absent.

If you are interested in PARP inhibitors, you should speak with your oncologist to see if you are eligible for any of the current trials.

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