Epigenome-Based Personalized Medicine in human Cancer

Figures & data

Figure 1.  The epigenetic transcriptional ‘machinery’.

BET, SEC: representative reader (proteins that bind modifications and facilitate epigenetic effects); HATs, DOT1L, DNMT, EZH2: representative writers (enzymes that establish DNA methylation or histone modifications); histone deacetylases, JmjC–KDMs, LSDs, DNA demethylase: representative erasers (proteins that remove DNA methylation or histone modification marks).

Table 1  Hypermethylated genes as predictors of chemosensitivity.

Gene name	Gene function	Tumor type application	Chemosensitivity prediction	Ref.
MGMT	DNA repair	Glioma, colon, lung, lymphoma	Sensitive to temozolomide, BCNU, ACNU, procarbazine	[20]
CHFR	Ubiquitin protein ligase	esophageal, gastric, cervical, lung, endometrial cancer and oral squamous cell carcinoma	Sensitive to paclitaxel and docetaxel	[24,28]
FANCF	DNA damage response	Ovarian	Sensitivity to cisplatin	[25]
BRCA1	DNA damage response	Breast, ovary	Sensitive to PARP inhibitors and alkylating agents	[29]
MLH1	DNA repair	Colon, stomach, endometrium, ovary	Resistance to cisplatin	[30]
GSTP1	Detoxification	Prostate, breast, kidney	Sensitivity to doxorubicin	[31]
PRKCDBP	Signal transduction	Colon	Resistance to TNF-α	[32]
SFN	Signal transduction	Lung	Sensitive to cisplatin and gemcitabine	[33]
TFAP2E	Transcriptional regulator	Colon	Sensitivity to fluorouracil	[34]
ABCB1	Protein transport	Breast	Sensitivity to doxorubicin	[35]
APAF1	Apoptotic activator	Melanoma	Resistance to adriamycin	[36]
CDK10	Cell cycle control	Breast	Resistance to anti-estrogens	[37]
IGFBP3	Signal transduction	Lung	Resistance to cisplatin	[38]
MT1E	Antioxidant	Melanoma	Sensitivity to cisplatin	[39]
TGM2	Apoptosis	Lung, breast, ovary	Resistance to doxorubicin and cisplatin	[40]
TP73	Stress response	Renal, melanoma	Sensitivity to cisplatin	[41]

Table 2  Representative inhibitors of key epigenetic regulators.

Category	Target enzyme	Compounds	Tumor type	Phase	Ref.
Writers	DOT1L	EPZ-5676	Hematological malignancies	Clinical trials	[68]
	EZH2	EPZ-6438	Advanced solid tumors, B-cell lymphoma	Clinical trials	[69]
		DZNep	Breast, colon and prostate cancer	Preclinical	[70]
Erasers	LSD1	ORY-1001	Relapsed or refractory acute leukemia	Clinical trials	[71]
		GSK2879552	Small-cell lung carcinoma	Clinical trials	[72]
Readers	BET	I-BET762	Hematological malignancies, NUT midline carcinoma, solid tumors	Clinical trials	[73]
		JQ1	MLL-rearranged leukemia, multiple myeloma	Preclinical	[74,75]

NUT: Nuclear protein of the testis.

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