PARP

PARP, poly (ADP-ribose) polymerase, is a term used to describe a family of proteins that play an important role in various cellular processes and are sometimes the target of new therapies. PARPs catalyze the transfer of ADP-ribose to other targeted proteins in order to mediate certain DNA activity, including:

  • DNA repair
  • Modulation of chromatin structure (the formed DNA/protein complex)
  • Transcription
  • Replication
  • Recombination

In targeting cancer and other diseases, PARP inhibitors are used to suppress these activities in the DNA of tumor cells. In particular, certain tumors rely on the role of the PARP proteins in repairing DNA for their survival; introducing PARP inhibitors can increase the tumor’s susceptibility to injury. Furthermore, PARP inhibitors have been shown to improve a tumor’s sensitivity to specific DNA-damaging therapies used in cancer treatments. On the other end of the spectrum, hyperactivation of the PARP pathway can stimulate programmed cell death and may be exploited to kill specific cancer cells. Thus, the PARP pathway offers a number of therapeutic intervention opportunities to stop the growth of cancer as well as inhibit other disease states. PARP is currently being used as a targeted therapy for breast cancer and ovarian cancer, and is being tested for other clinical applications including:

  • DNA repair mechanisms
  • Genetic defects of DNA repair
  • Clinical efficacy and toxicity
  • Identifying biomarkers and target tumors
  • Inducing tumor sensitivity
  • Overcoming PARP inhibitor resistance
  • Development of new agents