Table 1.
Perspectives for eluding resistance to PARP inhibitors. Potential strategies to enhance the efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in treatment-resistant tumors.
| Perspectives for Eluding PARPI Resistance | |
|---|---|
| Suppression of Alternative HR Pathways | |
| Suppression of mutator phenotype | Loss of RNF168 |
| POLQ inhibition by novobiocin kills HR deficient tumors in vitro/in vivo | |
| Indirect inhibition of HR | CONCERTO trial: cediranib + olaparib |
| AKT inhibitor: capivasertib + olaparib | |
| ceralasertib + olaparib | |
| Immunotherapy in HRD deficient cancers | durvalumab + olaparib + bevacizumab (AGO-DUO) (BOLD) |
| durvalumab + olaparib + cediranib | |
| pembrolizumab + olaparib (ENGOT ov43) | |
| pembrolizumab + niraparib (TOPACIO) | |
| atezolizumab + niraparib (ANITA) | |
| nivolumab + rucaparib (ATHENA combo) | |
| dostarlimab + niraparib (MITO33) (MOONSTONE) (ROCSAN) | |
| dostarlimab + niraparib + bevacizumab (OPAL) tremelimumab + olaparib | |
| tremelimumab + durvalumab + olaparib | |
| Abrogation of cell-cycle checkpoint signalling | EFFORT trial: adavosertib (WEE1 inhibitor) + olaparib |
| SOLAR trial: selumetinib (MEK inhibitor) + olaparib | |
| Targeting acquired vulnerabilities | Ioniziting radiation |