The Simulated Cell™ identifies LIG4 as a novel target in PARPi resistance via the modulation of NHEJ deficiency

Poly (ADP-ribose) polymerase (PARP) is a key enzyme in DNA repair and an approved target in various homologous recombination (HR)-deficient tumors, including breast, ovarian, pancreatic and lung cancer. However, after initial responsiveness, tumors often develop resistance toward PARP inhibitors (PARPi). One of the major mechanisms of PARPi resistance is the suppression of the non-homologous end joining (NHEJ) pathway. The major aim of our study was to find a novel target to overcome PARPi resistance.