fig2

Figure 2. Mechanisms of PARPi resistance. A: Efflux of PARP inhibitors by P-gp pumps may contribute to resistance by reducing the intracellular PARPi concentration; B: PARP1 deletion or point mutations in PARP1 reduce sensitivity to PARPi. PARG suppression restores downstream PARP1 signalling with PARPi therapy; C: loss of expression of PTIP, EZH2, MUS81 or increased miR-493-5p results in stabilization of the replication fork, leading to PARPi resistance; D: deficiency of 53BP1, RIF1, REV7 and RINN1-3 involved in the regulation of DNA end-resection during DNA repair may induce PARPi resistance; E: overexpression of miR-622 suppresses NHEJ and rescues the homologous recombination deficiency of BRCA mutated cells. Modified from Thomas et al.^[30]. PARP1: poly(ADP) ribose polymerase 1; NAD: nicotinamide adenine dinucleotide; PARG: poly(ADP) ribose glycohydrolase; HR: homologous recombination; NHEJ: non-homologous end joining; DNA: deoxyribonucleic acid