PARP1 and cancer: Nevertheless, this would suggest synergy between PARP inhibition (or a deficiency in PARP-1 protein) and CDD induced by high-LET IR in promoting cancer cell killing, similar to the concept of synthetic lethality observed with PARP inhibitors in combination with BRCA (DSB repair)-deficient cancers.23, 24 These data also correlate with our previous evidence demonstrating that CDD induced by high-LET protons appears to be largely single-strand break in nature and thus dependent on PARP-1, and predictably other single-strand break repair proteins, for repair.10