Preclinical Chemosensitization by PARP Inhibitors

Preclinical research has provided a strong rationale for employing PARP inhibitors (PARPi) as chemosensitisers in combination with cytotoxic agents, radiosensitisers in combination with radiation, as well as monotherapy to induce synthetic lethality in human malignancies. The primary aim of this chapter is to describe the rationale and preclinical pharmacology of potent PARPi (such as veliparib, rucaparib and olaparib) as chemosensitisers studied in cytotoxic combination regimens. Additional aims are to review: (1) emerging strategies for employing PARPi as monotherapy to induce synthetic lethality; and (2) potentially novel mechanisms by which PARPi may enhance antitumour therapy.