PCMdb: Pancreatic Cancer Methylation Database

Drug Resistant Methylated Genes

Here we are providing methylation status of genes. These genes methylation have been reported to be involved in drug resistance. For more information, please click HERE .

Gene Name	Gene Function	Drug Sensitivity	Methylation Status	Reference	Explanation
ABCB1	Protein Transport	Sensitivity to Doxorubicin	Hypermethylated	16356834	Doxorubicin is a DNA intercalator. Methylation of ABCB1 or GSTP1 promoter enhanced patient survival possibly by prolonged availability and activity of the drug.
BRCA1	DNA Damage Response	Sensitivity to PARP inhibitors and alkylating agents	Hypermethylated	20679605	BRCA1 is involved in DNA double strand break repair using homologous recombination. PARP inhibitors block PARP that repairs single strand DNA breaks. Hence, in BRCA1 expression deficient cells that could be due to BRCA1 hypermethylation, blocking the alternative DNA repair pathway involving PARP leads to accumulation of DNA lesions ultimately causing cell death.
CHFR	Ubiquitin Protein Ligase	Sensitivity to Paclitaxel and Docetaxel	Hypermethylated	12810945	CHFR protein functions in mitotic checkpoint pathway which gets impaired if CHFR is not expressed due to methylation. Due to this mitosis increases as seen in cancerous conditions. Docetaxel and Paclitaxel are mitotic inhibitors that block microtubule formation thus being effective in cancer if CHFR expression is low.
ESR1	ER signalling	Resistance to anti-oestrogens	Hypermethylated	17178894	Antiestrogen drugs that target estrogen receptor proteins derieved from genes like ESR1 engenders hypermethylation and hypomethylation of genes acting in the downstream pathway of ESR signalling. Among the genes that get hypomethylated are some oncogenes whose expression gets increased thereby causing cancer progression and antiestrogen resistance.
GSTP1	Detoxification	Sensitivity to Doxorubicin	Hypermethylated	20338046	Doxorubicin is a DNA intercalator. Methylation of ABCB1 or GSTP1 promoter enhanced patient survival possibly by prolonged availability and activity of the drug.
IGFBP3	Signal Transduction	Resistance to Cisplatin	Hypermethylated	20023704	Reduced IGFBP-3 expression effected by promoter-hypermethylation caused by cisplatin results in a reduction of tumor cell sensitivity to this drug.
MGMT	DNA repair	Sensitivity to Temozolomide,BCNU,ACNU,Procarbazine	Hypermethylated	11070098	Transfer of alkyl groups to MGMT (DNA repair enzyme) by alkylating agents prevents the formation of lethal cross-links in DNA leading to cell survival and cancer progression. Hence, suppression of MGMT expression by hypermethylation leads to sensitivity to alkylating drugs in cancers.
MLH1	DNA repair	Resistance to Cisplatin	Hypermethylated	10327053	MLH1 gene is involved in strand specific DNA mismatch repair. Cisplatin is known to cause hypermethylation of many genes. Thus an already hypermethylated status of MLH1 and its underexpression in cancer makes cisplatin ineffective.
SFN	Signal Transduction	Sensitivity to Cisplatin and Gemcitabine	Hypermethylated	16361617	SFN product 14-3-3sigma protein has a role in mitotic checkpoint as well as anti-apoptotic role of sequestering pro-apoptotic protein bad. Low expression by hypermethylation of this gene renders the cell susceptible to anti-cancer drugs.
TFAP2E	Transcriptional Regulator	Sensitivity to Fluorouracil	Hypermethylated	22397669	TFAP2E hypermethylation and its underexpression leads to increased expression of DKK4 that has been associated with carcinogen and fluorouracil.