PARP inhibitors are not all equal.

To many investigators PARP1 is simply a substrate for caspase 3, and whose cleavage is thought indicative of apoptosis. However, in reality PARP1 plays a major role in the biology of the cell cycle and DNA repair. (1)(,) (2) PARP1 binds to damaged DNA where it becomes enzymatically activated and ADP ribosylates itself and other proteins. PARP facilitates DNA repair complex formation, e.g., with BRCA1/2, and the activation of the cell cycle regulatory enzymes ATM and ATR. (2) PARP inhibitors as a single agent have only shown any degree of efficacy in breast and ovarian cancer patients who lack BRCA1/2 function. (3)(,) (4) The present studies examined PARP1 inhibitor biology in a range of triple negative and non-triple negative breast cancer cell lines.