Colon cancer stemness as a reversible epigenetic state: Implications for anticancer therapies

Table 1 Negative correlation between combined expression of cancer stem cell markers CD133, CD44 and CD166 and epigenetic writers

Family/gene symbol	Epidrug/chemical probe	Clinical trials for CRC	Results/status	Z-score	P value
DNA methyltransferases	5-azacytidine (Vidaza)1	Early Phase I to phase II[63,64]	No OR[63,65]
	5-aza-2’-désoxycytidine (Decitabine)1	Phase I to phase II[66-68]	No OR[66]; beneficial with Panitumumab[68]
	EGCG (Green tea extract)	Preclinical spheroid-derived cancer stem cell xenograft models[69]	Sensitization to chemotherapy
	Zebularine	Preclinical xenografts[70]	Anticancer activity
	RG108, Procainamide2
DNMT3A, DNMT3B, DNMT3L				-2.788/-4.848/-4.321	< 0.005
Activating Lysine methyltransferases
SETD6	vp22-RelA302-3163[71]			-4.641	3.47E-06
SETD1A				-4.375	1.212E-05
Repressive Lysine methyltransferases
SMYD5	-			-4.514	6.371E-06
EHMT2	UNC02243, UNC06423, BIX-012943			-4.322	1.545E-05
SETDB2	-			-3.6	0.0003176
PRDM13	-			-3.442	< 0.005
SUV39H1, SUV39H2	Chaetocin3			-3.422/-2.934	0.0006216
PRDM12	-			-3.089	0.00201
EZH1	UNC19993			-2.787	0.005314
EZH2	CPI-12052,4, EPZ-6438 (Tazemetostat)2, DZNep2, UNC19993			-2.495	0.01259
Arginine methyltransferases
CARM1	MS0493, SGC20853, TP-0643[72]			-3.812	0.0001381
PRMT1	MS0233[72]			-3.659	0.0002534
PRMT6	MS0233, MS049c, EPZ0204113[72], 6′-methyleneamine sinefungin3[73]			-3.521	0.0004301
Histone acetylation
KAT2A	CPTH23[74], γ-butyrolactone3 (MB-3)[75]			-4.683	2.823E-06
NAA10, NAA16, NAA20, NAA38, NAA40	-			-4.335/-3.255/-3.786/-3.801/-2.665	< 0.01
NAT8, NAT9	-			-2.573/-3.995	< 0.01
NCOA5, NCOA6	-			-3.238/-3.112	< 0.002
Histone phosphorylation
BAZ1B	-			-2.374	0.01758
Histone glycosylation
OGT	-			-3.172	0.001512

¹Approved for the treatment of other diseases;

²Used in clinical trials for other diseases;

³Not yet used in clinical trials;

⁴Activator. CRC: Colorectal cancer; OR: Objective response.