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

Table 2 Negative correlation between combined expression of cancer stem cell markers CD133, CD44 and CD166 and epigenetic erasers

Family/gene symbol	Epidrug/chemical probe	Clinical trials for CRC	Results	Z-score	P value
Histone deacetylation (Zinc-dependent)
	Acide valproïque1	I to II	In combination: OR in 64% patients or SD[76,77]
	Belinostat2, Apicidin3
	Entinostat	I to I/II	No OR[78] or SD[79]
	Panobinostat	I	PR and SD in combination with Bevacizumab[80]
	Vorinostat (SAHA)	I to II	No OR[81,82]; SD and PR with Bortezomib or 5FU and leucovorin or Doxorubicin[83-85]
	Trichostatine A2
	Mocetinostat2
	Sodium phenylbutyrate2	I	In combination with 5-FU: SD[86]
Class I	Romidepsin (Istodax)1	II	Ineffective[86]
	CI-994	I	PR in combination with carboplatin and placlitaxel[87]
HDAC8	TM-2-514, CUDC-1012, Pracinostat2, Ricolinostat2, Citarinostat2, Abexinostat2, Quisinostat3, PCI-340513			-2.527	0.0115
Class IIa (1 catalytic site, mainly cytoplasmic)
HDAC5	CUDC-1012, Pracinostat2, Domatinostat2, Quisinostat3, LMK-2353, TMP1953, TMP2693			-4.133	3.581E-05
Class IIb (2 catalytic sites, mainly cytoplasmic)
HDAC10	CUDC-1012, CUDC-9072, Pracinostat2, Domatinostat2, Abexinostat2, Tucidinostat2, Quisinostat3			-3.17	0.001525
Histone deacetylation NAD+ dependent (Class III)
	Resveratrol4	I	Reduced cell proliferation[88]
	Salermide3[89]
SIRT6	OSS_1281673			-3.467	0.0005257
SIRT7				-2.582	0.009835
Histone demethylation
LSD family of demethylases
	ORY-10013, (±)-tranylcypromine3
KDM2B	-			-3.54	0.0004003
KDM4D	-			-2.704	0.006848
JmjC containing lysine demethylases
	JIB-043
JMJD6	IOX13			-2.59	0.00961
JMJD5	IOX13			-2.588	0.009654

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; SD: Stable disease; PR: Partial response.