Table 2.

Current promising therapeutic approaches targeting DNA repair system in OvC.

DNA Repair Pathway	Gene Targets	In Vitro/In Vivo Efficiency	Pre-Clinical/Clinical Studies
Base Excision Repair	PARPi	Talazoparib and veliparib are in advanced clinical trials at the moment. Clinically available PARPi olaparib, rucaparib and niraparib are currently approved for the therapy of OvC on the basis of their BRCA1/2 status (summarized in [210])	Olaparib-approved by FDA and EMA for use in OvC therapy [144] Rucaparib-approved by FDA and EMA for use in OvC therapy [144] Niraparib-approved by FDA and EMA for use in OvC therapy [144] Veliparib–advanced clinical trials in combination with carboplatin and paclitaxel. Veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer PFS than carboplatin plus paclitaxel induction therapy alone [193,194] Talazoparib–ongoing advanced clinical trials [194,195]
Cell cycle checkpoints	CHEK1i	The CHEK1i V158411, PF-477736 and AZD7762 inhibited the proliferation of OvC cells [202] AZD7762 in combination with cisplatin suggested synergistic effects in ovarian clear cell carcinoma cell lines in vitro and suppressed growth of tumors in vivo [203] Prexasertib–effective in monotherapy in PARPi-resistant HGSOC cell lines and mouse xenografts [204] Combination of prexasertib mesylate monohydrate (LY2606368), a CHEK1 and CHEK2 inhibitor, and a PARPi, olaparib synergistically decreased cell viability in HGSOC cell lines (OVCAR3, OV90, PEO1 and PEO4) cell lines and induced greater DNA damage and apoptosis than the control and/or monotherapies [204,211]	Prexasertib–effective in clinical phase II study in recurrent HGSOC [201]
	ATRi	ATRi (VE-821, VE-822, AZ20) resensitized PARPi-resistant BRCA1-mutated human OvC cell line to PARPi [206] AZD6738 efficient in in ATM-deficient cells and in vivo in PDX mouse models with complete ATM loss [208] Combination PARPi with ATRi (AZD6738) and CHEK1i (MK8776) is more effective than PARPi alone in reducing tumor burden in BRCA1/2 mutated HGSOC cells and PDX models [209]	Ongoing clinical PhaseII CAPRI Study of ATRi AZD6738 (ceralasertib) in combination with PARPi olaparib in HGSOC patients [212]
	ATMi	ATMi KU55933 enhanced the response to ionizing radiation in A2780 and OVCAR3 OvC cells [213]
	WEE1i	Adavosertib (AZD 1775 alias MK1775)–efficient in vitro in SKOV-3 and ID8 OvC cell lines, efficient in vivo in ID8 ovarian tumors in monotherapy independent on TP53 or BRCA1 status [214]	AZD1775–active in phase I clinical study of monotherapy in OvC patients carrying BRCA mutations [215] AZD1775–combination therapy with AZD1775 enhanced carboplatin efficacy in TP53-mutated ovarian tumors in phase II clinical study [216]