PARP inhibitors are not all equal

摘要

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. PARP1 binds to damaged DNA where it becomes enzy-matically 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. PARP inhibitors as a single agent have only shown any degree of efficacy in breast and ovarian cancer patients who lack BRCA1/2 function. The present studies examined PARP1 inhibitor biology in a range of triple negative and non-triple negative breast cancer cell lines.