Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) are promising cancer treatments because they block a cell’s ability to repair DNA damage. Four PARPis are currently approved for use in the clinic, and more than 200 others are making their way through (pre)clinical phases.1 However, the ability of these anticancer therapies to effectively and specifically eliminate malignant cells depends on several factors that scientists should keep in mind during the screening and drug development process.
Maintaining genomic integrity is critical for cell survival. For this reason, at least 150 different proteins form an intricate DNA damage response (DDR) network that constantly scans and repairs a cell’s genome.2 PARP1 is one of the first responders to damaged DNA, and its importance is reflected in its abundance: this enzyme is one of the most common nuclear proteins.3 When PARP1 binds damaged DNA, it adds poly(ADP ribose) (PAR) chains to its own protein backbone and to ...
