TABLE 3.

The summary of the potential methylation therapy.

Method	Related gene	Function	Advantages and disadvantages	References
Combine chemoradiation therapy with DAPK1 gene target	DAPK1	Suppress the proliferation of tumor cells and induce apoptosis and autophagy	Advantages: Decrease side effects Disadvantages: Not mentioned	Bhattacharjee et al., 2018; Huang et al., 2018; Ren et al., 2018; Sood et al., 2018; Wang et al., 2018; Yadav et al., 2018
Combine chemoradiation therapy with BRCA1 gene target	BRCA1	DNA damage repair, transcriptional regulation and apoptosis	Advantages: Decrease side effects Disadvantages: The overexpression of BRCA1 gene may improve tumorigenesis	Li et al., 2018a; Maresca et al., 2018; Sood et al., 2018; Sun et al., 2018
Combine chemoradiation therapy with MGMT gene target	MGMT	Repair cytotoxic lesions by removing the methyl adducts from DNA	Advantages: Decrease side effects Disadvantages: Not mentioned	Jiapaer et al., 2018; Ren et al., 2018; Scicchitano et al., 2018; Sood et al., 2018; Yuan et al., 2018
Menthol	FANCF	Reverse the hypermethylation of FANCF promoter	Advantages: Menthol has high solubility and bioavailability Disadvantages: Not mentioned	Parashar et al., 2017
EGCG with eugenol-amarogentin	LimD1 and P16	Suppress proliferation and induce apoptosis through promoting the hypomethylation of LimD1 and P16 promoters	Advantages: More effective Disadvantages: Not mentioned	Pal et al., 2018
Combine chemoradiation therapy with STK31 gene target	STK31	Suppress migration and invasiveness and induce apoptosis	Advantages: Increase the efficacy of chemoradiation and reduce chemoresistance Disadvantages: Epigenetics drugs have many restrictions	Yin et al., 2016
Quercetin	TSG	Downregulate the levels of global DNA methylation and reverse the hypermethylation of TSG promoter	Advantages: Natural and fewer side effects Disadvantages: Low bioavailability	Kedhari Sundaram et al., 2019
Limoniastrum guyonianum aqueous gall extract (G extract) and luteolin	p16INK4A	Suppress the proliferation and induce apoptosis by activating p16INK4A-dependent cell cycle checkpoint signaling pathway	Advantages: Natural and fewer side effects Disadvantages: Not experiment in vivo and have no idea if it works for patients	Krifa et al., 2013