PARP Inhibition

Similarly, PARP proteins (poly (ADP-ribose) polymerase) proteins are involved in multiple DNA repair processes and have been targeted through inhibition for the treatment of ovarian cancer. The PARP inhibitors that have been approved by the FDA have been shown to prevent breaks in single-stranded DNA (which have been affected by the BRCA mutation causing the onset of cancer) so that the enzyme PAR encourages the mitochondrial release of AIF; therefore leading to apoptosis of the cells affected by the cancer mutations. This therapy has been hypothesized to be combined with Bcl-2 inhibition, which is a family of proteins involved in regulating apoptotic pathways. The therapy hypothesized therapy focuses on PARP inhibition in conjunction with the increased inhibition of anti-apoptotic proteins from the Bcl-2 family, specifically BH3. The Bcl-2 inhibition therapy currently under clinical trial is the ABT-263 monotherapy, and has shown clinically significant results in competing with BH3 proteins for binding with anti-apoptotic proteins and preventing those proteins from inactivating pro-apoptotic proteins. In vitro, the combined therapy displayed increased caspase activity and encouraged the Bax/Bak apoptosis pathway (Yokohama, 2017).