Endogenous retroviruses in the origins and treatment of cancer

Table 2 Therapeutic agents shown to stimulate ERV expression in preclinical models of cancer

Compound	Target	Cancer model	Possible ERV-related clinical effects	References
5-azacytidine 5-aza-2-deoxycytidine (5-aza-CdR)	DNMT1	Epithelial ovarian cancer cell lines B16-F10 mouse melanoma model Colorectal cancer cell line	dsRNA mediated viral mimicry Sensitizes cells to checkpoint inhibitor α-CTLA-4	[101, 102]
GSK-LSD1	LSD1 (KDM1A)	Breast cancer cell line B16 mouse melanoma model	dsRNA viral mimicry Sensitizes cells to checkpoint inhibitor α-PD-1	[103]
Vorinostat Pracinostat + 5-aza-CdR	pan-HDAC HDAC class I/II/IV HDAC + DNMT1	Lung cancer cell line	Activates ERV cryptic transcription start sites Stimulates interferon response	[42]
GSK126 GSK343	EZH2	Resistant chemorefractory small-cell lung cancer Taxane-resistant triple negative breast cancer cell lines	Promotes dsRNA production Alters innate immune signalling and promotes EMT Induces viral mimicry	[104, 105]
UNC0638 + 5-aza-CdR	G9a + DNMT1	Ovarian cancer cell lines	Induces viral mimicry	[106]
MC180295	CDK9	Colorectal cancer cell line Ovarian cancer cell line injected into mice	Induces viral mimicry Sensitizes cells to checkpoint inhibitor α-PD-1	[107]
Abemaciclib	CDK4/6	Mouse breast cancer models	Inhibits DNMT1 expression thereby inducing viral mimicry	[108]
Vitamin C	TET enzymes	AML, colorectal, breast, and liver cancer cell lines	Induces viral mimicry	[109]
RRX-001	Hemoglobin	Colon cancer cell lines	Decreases DNMT expression to induce viral mimicry	[110]

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