The Mechanism of Action of Olaparib

July 30, 2013
Jane Robertson, MD

Jane Robertson, MD, Global Product Vice President at AstraZeneca, describes the mechanism of action of the PARP inhibitor olaparib.

Jane Robertson, MD, Global Product Vice President of Oncology at AstraZeneca, describes the mechanism of action of olaparib, a PARP inhibitor.

The enzyme PARP is important for repairing single strand DNA breaks. If PARP is inhibited, single strand breaks cannot be repaired efficiently. Robertson explains that as the cell goes through cell division, these breaks become double strand breaks, which are lethal to cells, Robertson says. Eventually, this causes cumulative DNA damage and the cell dies.

Clinical Pearls

Normal cells, however, have a good pathway (the homologous recombination pathway) to repair double strand breaks. Some types of tumor cells have a deficiency in this homologous recombination pathway. Robertson said the best example of this phenomenon is the deficiencies that can occur in BRCA1 and BRCA2.

  • Olaparib is a PARP inhibitor
  • Inhibiting PARP causes cumulative DNA damage and cell death
  • Some types of tumor cells have a deficiency in the homologous recombination pathway