Poly (ADP-ribose) polymerase, or PARP, is a protein that serves several roles in the cellular processes, including DNA repair and programmed cell death. Normal cells use PARP to repair DNA damaged by radiation and toxins in the environment to live out their normal life cycle. Some cancers use PARP to repair DNA damage caused by treatments like chemotherapy and radiation, thus extending their uncontrolled growth. Cancers that use PARP to their advantage can become highly resistant to treatment.

A PARP inhibitor is a drug that blocks PARP proteins from repairing damaged DNA in cancer cells. Chemotherapy and radiation both work by damaging the DNA of cancer cells so that they either die or do not reproduce. Many types of cancers use PARP enzymes to repair their DNA damage and recover from the assault of cancer treatment. If a PARP inhibitor is added to chemotherapy, researchers hope that cancers resistant to anti-cancer drugs will become vulnerable to fatal DNA damage.

The BRCA1 and BRCA2 genes are important for the repair of DNA double-strand breaks by a mechanism called homologous recombination. When the function of these genes is lost, cells are unable to repair damage to their DNA and this predisposes the individual to breast, ovarian and other cancers. Researchers have recently found that cells deficient for either BRCA1 or BRCA2 are particularly sensitive to the inhibition of PARP enzymatic activity; this results in chromosomal instability, cell cycle arrest and subsequent programmed cell death. Researchers reported in 2008 very promising data from a Phase I clinical trial using a PARP inhibitor alone in patients with BRCA1 or BRCA2 mutations, suggesting a potential therapeutic role as a single agent in this targeted patient population.

Clinical trials are currently ongoing to assess the efficacy of PARP inhibitors both as single agents and in-combination with other treatments.

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