Second, we provided evidence of a crucial role of PARP1 in CRC-SCs exhibiting low constitutive RS coupled to high resistance to (i) replication poisons including the standard CRC chemotherapeutic irinotecan, and (ii) ATR/CHK1 inhibitors including prexasertib (here dubbed CHK1i) and berzosertib which are under clinic investigation (https://clinicaltrials.gov). Here, ATR is linked to colorectal carcinoma.