ATR and colorectal carcinoma: As a further limitation of these strategies, we recently revealed a mechanism of resistance to ATR-CHK1 inhibitors in CRC-SCs based on upregulation of poly(ADP-ribose) polymerase 1 (PARP1) [26], a DDR player with pleiotropic roles in DNA damage repair, the response to replication stress, and regulated cell death [27].