PolyADP-ribose polymerase (PARP) plays a key role in the repair of DNA single-strand breaks. In the presence of the PARP inhibitor olaparib, single-strand breaks accumulate. When a replication fork encounters a single- strand break, it converts it to a double-strand break, which in normal cells is then repaired by homologous recombination. In cells defective for homologous recombination, however, inhibition of PARP triggers cell death.

Patients who have only one functional copy of the Brca1 gene, which is required for homologous recombination, are at much higher risk for cancer of the breast and ovary. Cancers that arise in these tissues in these patients can be treated successfully with olaparib. Explain how it is that treatment with olaparib kills the cancer cells in these patients, but does not harm their normal cells.