Epigenetic synthetic lethality approaches in cancer therapy

Clinical Epigenetics

Table 1 Epigenetic-related synthetic lethal relationships and mechanisms in different

Gene	Inhibitor	Cancer type	Mechanism	References
Epigenetic alterations with epigenetic inhibitors
ARID1A	EZH2 i	OCCC	Epigenetic antagonism with PRC2	[11]
SMARCB1	EZH2 i	MRTs and ATRT	Restores expression of p16^INK4a	[17, 20]
SMARCB1	HDAC i	MRTs and ATRT	Mimics HAT activity	[16]
CREBBP	p300 i	Lung Cancer Hematopoietic cancer	Reduces acetylation of MYC promoter	[23]
MLL	DOT1L i	Leukemia (MLL)	Reduces H3K79 methylation levels, interfering expression of MLL-fusion target gene inhibit LAMP5 and promote autophagy	[34,35,36,37,38]
Epigenetic alterations with non-epigenetic inhibitors
SETD2	WEE1 i	Kidney cancer mast cell leukemia	Starves the cells of dNTPs	[40, 46]
SETD2	PI3Kβ-AKT i	Kidney cancer	Inhibition of the PI3Kβ-AKT axis	[50]
KMT2C	PARP i	Bladder cancer Colon cancer NSCLC HNSCC	Blocks HR-mediated DNA repair	[58]
Non-epigenetic alterations with epigenetic inhibitors
TP53	EZH2 i	Breast cancer Prostate cancer	Blocks the binding of EZH2 and p53	[64]

ISSN: 1868-7083