Table 2 The feasible combination therapy to enhance PARPi sensitivity and overcome PARPi resistance
From: PARP inhibitor resistance: the underlying mechanisms and clinical implications
Combination therapy | Trials | NCT | Phase | Treatment | Status | Study population |
|---|---|---|---|---|---|---|
PARPi-oHSVs combination | No | Â | Â | Â | Â | Â |
PARPi-IR combination | Yes | NCT00649207 | I | Veliparib + WBRTa | Completed | Solid tumors with brain metastases |
PARPi-IR combination | Yes | NCT01264432 | I | Veliparib + IR | Completed | Peritoneal carcinomatosis; fallopian tube, ovarian and primary peritoneal cancers |
PARPi-IR combination | Yes | NCT01589419 | I | Veliparib + capecitabine + IR | Completed | Locally advanced rectal cancer |
PARPi-IR combination | Yes | NCT02412371 | I/II | Veliparib + Paclitaxel/Carboplatin + IR | Completed | Stage III NSCLCb |
PARPi-IR combination | Yes | NCT01386385 | I/II | Veliparib + Paclitaxel/Carboplatin + IR | Active, not recruiting | Stage III NSCLC |
PARPi-IR combination | Yes | NCT01618357 | I | Veliparib + IR | Recruiting | Breast cancer |
PARPi-CDKi combination | No | Â | Â | Â | Â | Â |
PARPi-immunotherapy | Yes | NCT02734004 | I/II | Olaparib + MED14736 | Active, not recruiting | Ovarian, breast, SCLC cand gastric cancers |
PARPi-immunotherapy | Yes | NCT03824704 | II | Rucaparib + Nivolumab | Active, not recruiting | Epithelia ovarian cancer, fallopian tube cancer, primary peritoneal cancer, HGSCd and endometrioid adenocarcinoma |
PARPi-immunotherapy | Yes | NCT02849496 | II | Olaparib + Atezolizumab | Recruiting | Locally advanced unresectable; metastatic non-HER2-positive breast cancer |
PARPi- epigenetic drugs | No | Â | Â | Â | Â | Â |
PARPi- HSP90 inhibitors | No | Â | Â | Â | Â | Â |
PARPi-WEE1 inhibitors | Yes | NCT03579316 | II | Olaparib + AZD1775 | Recruiting | Recurrent fallopian tube, ovarian and primary peritoneal cancers |
PARPi-WEE1 inhibitors | Yes | NCT04197713 | I | Olaparib + AZD1775 | Not yet recruiting | Advanced solid tumors with selected mutations and PARP Resistance |
PARPi-WEE1 inhibitors | Yes | NCT02576444 | II | Olaparib + AZD1775 | Active, not recruiting | Tumors harboring either TP53 or KRAS mutations or mutations in KRAS and TP53 |
PARPi-WEE1 inhibitors | Yes | NCT02511795 | I | Olaparib + AZD1775 | Completed | Refractory solid tumors; Relapsed SCLC |
PARPi-ATR inhibitors | Yes | NCT02576444 | II | Olaparib + AZD6738 | Active, not recruiting | Tumors harboring mutations leading to dysregulation of the PI3K/AKT pathway |
PARPi-ATR inhibitors | Yes | NCT04065269 | II | Olaparib + AZD6738 | Recruiting | Gynaecological cancers |
PARPi-ATR inhibitors | Yes | NCT03787680 | II | Olaparib + AZD6738 | Recruiting | Prostate cancer |
PARPi-WEE1/ATR inhibitors | Yes | NCT03330847 | II | Olaparib + AZD6738/ AZD1775 | Recruiting | Metastatic triple negative breast cancer |
PARPi-ATR inhibitors | Yes | NCT03878095 | II | Olaparib + AZD6738 | Recruiting | IDH1 and IDH2 mutant tumors |
PARPi-ATR inhibitors | Yes | NCT03462342 | II | Olaparib + AZD6738 | Recruiting | HGSC |
PARPi-ATR inhibitors | Yes | NCT03428607 | II | Olaparib + AZD6738 | Active, not recruiting | SCLC |
PARPi-ATR inhibitors | Yes | NCT03682289 | II | Olaparib + AZD6738 | Recruiting | Clear cell renal cell cancer; Metastatic renal cell cancer; Metastatic urothelial cancer; Metastatic pancreatic cancer; Locally advanced pancreatic cancer |