Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOTV1FU)

• DOT Name: Melanoma-associated antigen B6 (MAGEB6)
• Synonyms: Cancer/testis antigen 3.4; CT3.4; MAGE-B6 antigen
• Gene Name: MAGEB6
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Esophageal adenocarcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Rectal adenocarcinoma
  Squamous cell carcinoma
  Metastatic malignant neoplasm
  Rectal carcinoma
  Gastric cancer
  Stomach cancer
• UniProt ID: MAGB6_HUMAN
• Pfam ID: PF01454 ; PF12440
• Sequence:
  MPRGHKSKLRTCEKRQETNGQPQGLTGPQATAEKQEESHSSSSSSRACLGDCRRSSDASI
  PQESQGVSPTGSPDAVVSYSKSDVAANGQDEKSPSTSRDASVPQESQGASPTGSPDAGVS
  GSKYDVAANGQDEKSPSTSHDVSVPQESQGASPTGSPDAGVSGSKYDVAAEGEDEESVSA
  SQKAIIFKRLSKDAVKKKACTLAQFLQKKFEKKESILKADMLKCVRREYKPYFPQILNRT
  SQHLVVAFGVELKEMDSSGESYTLVSKLGLPSEGILSGDNALPKSGLLMSLLVVIFMNGN
  CATEEEVWEFLGLLGIYDGILHSIYGDARKIITEDLVQDKYVVYRQVCNSDPPCYEFLWG
  PRAYAETTKMRVLRVLADSSNTSPGLYPHLYEDALIDEVERALRLRA
• Tissue Specificity: Expressed in testis. Not expressed in other normal tissues, but is expressed in tumors of different histological origins.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Esophageal adenocarcinoma	DISODWFP	Strong	Biomarker	[3]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[7]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[7]
Rectal adenocarcinoma	DIS8R9VO	Strong	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[9]
Metastatic malignant neoplasm	DIS86UK6	moderate	Genetic Variation	[10]
Rectal carcinoma	DIS8FRR7	Disputed	Biomarker	[11]
Gastric cancer	DISXGOUK	Limited	Biomarker	[12]
Stomach cancer	DISKIJSX	Limited	Biomarker	[12]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Melanoma-associated antigen B6 (MAGEB6).	[13]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Melanoma-associated antigen B6 (MAGEB6).	[14]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Melanoma-associated antigen B6 (MAGEB6).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Melanoma-associated antigen B6 (MAGEB6).	[16]

References

• [1] Reliability of clinical nodal status regarding response to neoadjuvant chemoradiotherapy compared with surgery alone and prognosis in esophageal cancer patients.Acta Oncol. 2019 Nov;58(11):1640-1647. doi: 10.1080/0284186X.2019.1648865. Epub 2019 Aug 9.
• [2] Drivers of 30- and 90-day Postoperative Death After Neoadjuvant Chemoradiation for Esophageal Cancer.Ann Thorac Surg. 2020 Mar;109(3):921-926. doi: 10.1016/j.athoracsur.2019.10.057. Epub 2019 Dec 14.
• [3] Neoadjuvant radiochemotherapy in adenocarcinoma of the esophagus: ERCC1 gene polymorphisms for prediction of response and prognosis.J Gastrointest Surg. 2012 Jan;16(1):26-34; discussion 34. doi: 10.1007/s11605-011-1700-x. Epub 2011 Sep 29.
• [4] Inflammatory cytokines are associated with response and prognosis in patients with esophageal cancer.Oncotarget. 2017 Jul 18;8(29):47518-47532. doi: 10.18632/oncotarget.17671.
• [5] A Comprehensive Expression Analysis of Cancer Testis Antigens in Head and Neck Squamous Cell Carcinoma Revels MAGEA3/6 as a Marker for Recurrence.Mol Cancer Ther. 2015 Mar;14(3):828-34. doi: 10.1158/1535-7163.MCT-14-0796. Epub 2015 Jan 6.
• [6] The prognostic role of FDG PET/CT before combined radio-chemotherapy in anal cancer patients.Ann Nucl Med. 2020 Jan;34(1):65-73. doi: 10.1007/s12149-019-01416-y. Epub 2019 Nov 14.
• [7] Genomic Validation of 3-Tiered Clinical Subclassification of High-Risk Prostate Cancer.Int J Radiat Oncol Biol Phys. 2019 Nov 1;105(3):621-627. doi: 10.1016/j.ijrobp.2019.06.2510. Epub 2019 Jul 2.
• [8] Association of Plane of Total Mesorectal Excision With Prognosis of Rectal Cancer: Secondary Analysis of the CAO/ARO/AIO-04 Phase 3 Randomized Clinical Trial.JAMA Surg. 2018 Aug 1;153(8):e181607. doi: 10.1001/jamasurg.2018.1607. Epub 2018 Aug 15.
• [9] C-myc gene amplification in different stages of oesophageal squamous cell carcinoma: prognostic value in relation to treatment modality.Anticancer Res. 2003 Mar-Apr;23(2B):1489-93.
• [10] Pattern of node metastases in patients treated with radical cystectomy and extended or superextended pelvic lymph node dissection due to bladder cancer.Urol Oncol. 2018 Jun;36(6):307.e9-307.e14. doi: 10.1016/j.urolonc.2018.03.002. Epub 2018 Mar 27.
• [11] Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer.J Clin Oncol. 2019 Jan 1;37(1):33-43. doi: 10.1200/JCO.18.00032. Epub 2018 Nov 7.
• [12] Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).BMC Cancer. 2018 Apr 20;18(1):450. doi: 10.1186/s12885-018-4367-9.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.