Table 2.

Recent examples of preclinical studies that have tested epigenetic inhibitors in gynaecological cancers.

Enzyme	Epigenetic Inhibitor	Combination Agent(s)	Cancer Type	Model/Cell Lines Tested	Inhibitor Dose and Treatment Duration	Outcome	Reference(s)
KMT4/DOT1L	EPZ004777	None	Ovarian	PEO1 and PEO4 cell lines	0.1 µM, 72 h	Growth arrest	[96]
EZH2	GSK126	Cisplatin	Ovarian	OVCAR3 and CA-MSC orthotopic mouse model	Various concentrations	Cell viability of OVCAR3 cells unaffected, but decreased ability of OVCAR3 cells to metastasise	[97]
EZH2	GSK126	5-AZA dC	Ovarian	NSG model	30 mg/kg, 3 times a week for 2 weeks	Increased efficacy of adoptive T-cell therapy in vivo	[58]
EZH2	GSK126	None, Cisplatin or Doxorubicin	Endometrial	Various cancer cell lines	0.025–20 µM, 8 days	Decreased cell proliferation and induction of apoptosis. Additive effects with cisplatin or doxorubicin	[98]
EZH2	DZNep	None	Cervical	HeLa and HeLa/DDP cells	Various concentrations, 72 h	Reversal of cisplatin resistance observed in the HeLa/DDP cell line	[99]
G9a (EHMT2)	BIX01294	None	Cervical	CaSki, HeLa and SiHa cell lines	5 µM, 72 h	Cell migration and invasion attenuated in BIX01294-treated cells	[100]
G9a (EHMT2)	BIX01294	None	Cervical	Subcutaneous SiHa cell line xenograft cervical cancer tumor model	5 mg/kg and 10 mg/kg, 39 days	Xenograft tumour growth significantly attenuated from day 29 at a dose of 10 mg/kg compared to control	[100]
G9a (EHMT2)	UNC0638	None	Ovarian	SKOV-3, ES-2, and PA-1 cell lines	2 µM, 48 h	Increase in metastasis suppressor genes such as CDH10	[101]
G9a (EHMT2)	UNC0638	None	Ovarian	SKOV-3 cell line	2 µM, 48 h	Decreased metastasis-related signaling	[17]
SUV39H1/SUV39H2	Chaetocin	None	Ovarian	OVCAR3 cell line	IC50–60.66 nM, 24 h	Inhibited proliferation, induced ROS accumulation and resulted in caspase-induced cell death in OVCAR-3 cells	[102]
SUV39H1/SUV39H2	Chaetocin	None	Cervical	HeLa and CaSki cell lines	150 nM, 24 h	Restored the innate immune response to exogenous DNA	[103]
KDM6A/6B	GSK-J4	None	Cervical	SiHa and HeLa cell lines	25–100 µM, 72 h	Decreased cell viability in SiHa cell line, no effect in HeLa cell line	[104]
KDM6A/6B	GSK-J4	None	Cervical	CaSki cell line	0–30 µM, 72 h	Decreased cell viability	[104]
KDM6A/6B	GSK-J4	None	Ovarian	A2780 cancer stem cell like cells	0.5–10 µM, 72 h	Decreased cell viability	[16]
LSD1	SP-2577	None	Ovarian	SWI/SNF-mutated cell lines	0.01–1.1 µM, 72 h	Affects cell viability, and induces expression of inflammatory cytokines in organoids	[105]
LSD1	HCI2509	None	Endometrial	AN3CA and KLE cell lines	IC50–500 nM, 96 h	Apoptotic cell death in cell lines, tumour regression in orthotopic xenografts	[19]
BRD4	JQ1, I-BET151	None	Ovarian	Various cell lines	0.01–10 µM	Cell cycle arrest in all subtypes of ovarian cancer cell lines tested	[32]
BRD4	JQ1	None	Ovarian	OVCAR-3 cell line xenograft and patient-derived xenograft model	50 mg/kg	Decreased tumour volume	[32]