Update on PARP inhibitor therapy for solid tumors

There are different types of DNA defects caused by chemicals and environmental factors which include single-strand break (SSB), mismatch repair (MMR), and double-strand break (DSB).1 Polyadenosine diphosphate [ADP] ribose polymerase-1 (PARP1) and -2 (PARP2) enzymes2 are responsible for repair of most of the SSB. After they detect the defective site, they bind to the DNA damage site and recruit a set proteins to repair the break.3,4 When those proteins are recruited to the damaged site, the PARP-DNA interaction becomes unstable so that DNA repair can proceed.5 If the SSB are not repaired, they are converted to DSB.6 In that situation, another repair mechanism called homologous recombination (HR) will play a role. This mechanism is well represented in PARP1 knockout mice that SSB could not be repaired, but HR repair and non-homologous end joining (NHEJ) pathways were able to repair the formed DSB (Figure 1). HR is slower than NHEJ, but it is more accurate.7