HPF1 and cancer: Since histone serine ADP-ribosylation is a key step in DDR8,9,13,16,26, and turning off PARP1/2 activity to inhibit the DNA damage response in tumor cells is a promising approach for cancer treatment, it is worthwhile to develop inhibitors targeting HPF1-dependent serine ADP-ribosylation, i.e. to consider the remodeled active site structure, instead of the open active site of PARP1/2 alone.