How does the combination of NUC-1031 and cisplatin affect cell cycle progression and DNA damage in cancer cells?

Both NUC-1031 and cisplatin cause cell cycle arrest and DNA damage, but their combined effects on these processes are not fully understood.

The combination of NUC-1031 and cisplatin significantly increases DNA damage and enhances cell cycle arrest compared to either agent alone. NUC-1031 causes prolonged S phase arrest and DNA damage response, while cisplatin primarily causes G2/M phase arrest. When combined, the drugs show additive effects on DNA damage markers such as p-ATM and γH2AX, and a synergistic effect on p-Chk1 phosphorylation. This suggests that the combination can lead to more effective cell cycle arrest and DNA damage, potentially enhancing the therapeutic efficacy in treating biliary tract and ovarian cancers.