Poly-ADP ribose polymerase (PARP) inhibitors are currently used in the treatment of several cancers carrying mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2, with many more potential applications under study and in clinical trials. Here, we discuss the potential for extending PARP inhibitor therapies to tumours with deficiencies in the DNA damage-activated protein kinase, Ataxia-Telangiectasia Mutated (ATM). We highlight our recent findings that PARP inhibition alone is cytostatic but not cytotoxic in ATM-deficient cancer cells and that the combination of a PARP inhibitor with an ATR (ATM, Rad3-related) inhibitor is required to induce cell death.
Cancers. 2020 Mar 14*** epublish ***
Nicholas R Jette, Mehul Kumar, Suraj Radhamani, Greydon Arthur, Siddhartha Goutam, Steven Yip, Michael Kolinsky, Gareth J Williams, Pinaki Bose, Susan P Lees-Miller
Department of Biochemistry and Molecular Biology, Robson DNA Science Centre, Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 1N4, Canada., Tom Baker Cancer Centre, 1331 29 St NW, Calgary, AB T2N 4N2, Canada., Cross Cancer Institute, 11560 University Avenue NW, Edmonton, AB T6G 1Z2, Canada.