Table 2.
The relevant drug resistance mechanism studies of different PARPi.
| Drug | Mechanism of PARPi resistance | Solution | Reference |
|---|---|---|---|
| Olaparib | Enhancement of drug efflux | p-glycoprotein inhibitor | Rottenberg, 200858 |
| BRCA reversal mutation | Inhibition of DNA end-joining repair pathways | Tobalina, 202165 | |
| Homologous recombination repair restoration | – | Mirman, 202271 | |
| High C/EBPβ expression induces restoration of HR capacity | Targeting C/EBPβ | Tan, 202175 | |
| Restoration of replication fork stability | – | Taglialatela, 201777 | |
| Promotes degradation of stalled replication forks | – | Rondinelli, 201778 | |
| The overexpression of High-mobility group box 3 (HMGB3) increased the insensitivity to PARPi, | Targeted inhibition of HMGB3 | Ma, 202289 | |
| Activates STAT3 | – | Martincuks, 202193 | |
| Clonal evolution | – | Anniina, 202194 | |
| Hypoxia | Eliminating hypoxic tumor cells | Mehibel, 202197 | |
| Rucaparib | BRCA reversal mutation | Improve the detection of mutations | Lin, 201967 |
| Promotes degradation of stalled replication forks | – | Rondinelli, 201778 | |
| Acquired RAD51C promoter methylation loss | – | Ksenija, 202182 | |
| Methylation of BRCA1 copies | quantitative BRCA1 methylation analysis | Kondrashova, 201882 | |
| Niraparib | Acquired RAD51C promoter methylation loss | – | Ksenija, 202183 |
| Clonal evolution | – | Anniina, 202194 | |
| Talazoparib | Homologous recombination repair restoration | – | Waks, 202065 |
| Clonal evolution | – | Anniina, 202194 | |
| Hypoxia | Eliminating hypoxic tumor cells | Mehibel, 202197 |