Details of the Drug Combination

General Information of Drug Combination (ID: DCADJTY)

• Drug Combination Name: Crizotinib + Epirubicin
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Crizotinib (DM4F29C): Small molecular drug
  Epirubicin (DMPDW6T): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T-47D
  Zero Interaction Potency (ZIP) Score: 5.02
  Bliss Independence Score: 11.33
  Loewe Additivity Score: 8.53
  LHighest Single Agent (HSA) Score: 9.3

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Crizotinib

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[2]

Crizotinib Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Modulator	[7]
ALK tyrosine kinase receptor (ALK)	TTPMQSO	ALK_HUMAN	Modulator	[7]
Proto-oncogene c-Ros (ROS1)	TTSZ6Y3	ROS1_HUMAN	Modulator	[7]
HGF/Met signaling pathway (HGF/Met pathway)	TTKA5LP	NOUNIPROTAC	Inhibitor	[8]

Crizotinib Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[10]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[10]

Crizotinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]

Crizotinib Interacts with 45 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[12]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[13]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Response To Substance	[5]
ALK tyrosine kinase receptor (ALK)	OTV3P4V8	ALK_HUMAN	Decreases Response To Substance	[14]
Prominin-1 (PROM1)	OTBHV8NX	PROM1_HUMAN	Decreases Expression	[4]
CD44 antigen (CD44)	OT9TTJ41	CD44_HUMAN	Decreases Expression	[4]
Epithelial cell adhesion molecule (EPCAM)	OTHBZK5X	EPCAM_HUMAN	Decreases Expression	[4]
Cytidine deaminase (CDA)	OT3HXP6N	CDD_HUMAN	Decreases Expression	[4]
Insulin-induced gene 1 protein (INSIG1)	OTZF5X1D	INSI1_HUMAN	Increases Expression	[15]
Acyl-CoA 6-desaturase (FADS2)	OTUX531P	FADS2_HUMAN	Increases Expression	[15]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[15]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Increases Expression	[15]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[15]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[15]
Sterol regulatory element-binding protein 2 (SREBF2)	OTBXUNPL	SRBP2_HUMAN	Increases Expression	[15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[15]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[15]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C)	OT6KFNMS	CAC1C_HUMAN	Decreases Activity	[15]
Sodium channel protein type 5 subunit alpha (SCN5A)	OTGYZWR6	SCN5A_HUMAN	Decreases Activity	[15]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[5]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[5]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Decreases Secretion	[16]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Decreases Secretion	[16]
Tyrosine-protein kinase Lck (LCK)	OT883FG9	LCK_HUMAN	Decreases Activity	[17]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[18]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[19]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[18]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[20]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[21]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[21]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[22]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[23]
Ras GTPase-activating-like protein IQGAP1 (IQGAP1)	OTZRWTGA	IQGA1_HUMAN	Decreases Phosphorylation	[24]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[23]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[5]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[25]
Echinoderm microtubule-associated protein-like 4 (EML4)	OTJC45TA	EMAL4_HUMAN	Increases Mutagenesis	[21]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Activity	[13]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[26]
Pro-epidermal growth factor (EGF)	OTANRJ0L	EGF_HUMAN	Decreases Response To Substance	[22]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Response To Substance	[26]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Response To Substance	[14]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Decreases Response To Substance	[22]
Protransforming growth factor alpha (TGFA)	OTPD1LL9	TGFA_HUMAN	Decreases Response To Substance	[22]

Indication(s) of Epirubicin

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[3]

Epirubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[27]

Epirubicin Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[28]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[29]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[29]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[29]

Epirubicin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[30]

Epirubicin Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[31]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[31]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[31]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Response To Substance	[32]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[33]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[34]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[35]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[36]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Affects Mutagenesis	[37]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[31]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Increases Phosphorylation	[38]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[38]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[38]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Mutagenesis	[37]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[39]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[34]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[34]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Increases Phosphorylation	[38]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[39]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[40]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Increases Response To Substance	[41]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)	OT9AGAIJ	LHPP_HUMAN	Increases ADR	[40]
Alpha-protein kinase 1 (ALPK1)	OTBW6SGD	ALPK1_HUMAN	Increases ADR	[42]
Baculoviral IAP repeat-containing protein 6 (BIRC6)	OTCQJAB0	BIRC6_HUMAN	Decreases Response To Substance	[43]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[44]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[45]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[46]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Response To Substance	[47]
Little elongation complex subunit 1 (ICE1)	OTOXTBUH	ICE1_HUMAN	Increases ADR	[40]
Microcephalin (MCPH1)	OTYT3TT5	MCPH1_HUMAN	Increases ADR	[42]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCPCONN	OVCAR3	Investigative	[48]
Adult T acute lymphoblastic leukemia	DC6WDN7	MOLT-4	Investigative	[48]
Amelanotic melanoma	DC8LF53	M14	Investigative	[48]
Astrocytoma	DCFSTQV	U251	Investigative	[48]
Clear cell renal cell carcinoma	DCD527H	CAKI-1	Investigative	[48]
Cutaneous melanoma	DCIUO2Y	SK-MEL-5	Investigative	[48]
Cutaneous melanoma	DC60HAJ	SK-MEL-28	Investigative	[48]
Glioma	DCRSUTD	SF-539	Investigative	[48]
High grade ovarian serous adenocarcinoma	DC4IQB6	NCI\\/ADR-RES	Investigative	[48]
Lung adenocarcinoma	DC4ZNSR	HOP-62	Investigative	[48]
Malignant melanoma	DCXIWF3	LOX IMVI	Investigative	[48]
Melanoma	DC84ONC	UACC-257	Investigative	[48]
Minimally invasive lung adenocarcinoma	DCTW6ZC	NCI-H322M	Investigative	[48]
Papillary renal cell carcinoma	DC488S2	ACHN	Investigative	[48]
Plasma cell myeloma	DCO05AN	RPMI-8226	Investigative	[48]
Breast adenocarcinoma	DCBFSJ0	MDA-MB-468	Investigative	[1]
Invasive ductal carcinoma	DC3XL78	BT-549	Investigative	[1]
Invasive ductal carcinoma	DCJUULH	HS 578T	Investigative	[1]

References

• [1] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4903).
• [3] New drugs for the treatment of cancer, 1990-2001. Isr Med Assoc J. 2002 Dec;4(12):1124-31.
• [4] Enhancement of the antiproliferative activity of gemcitabine by modulation of c-Met pathway in pancreatic cancer. Curr Pharm Des. 2013;19(5):940-50.
• [5] Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
• [6] Aberrant expression of the transcriptional factor Twist1 promotes invasiveness in ALK-positive anaplastic large cell lymphoma. Cell Signal. 2012 Apr;24(4):852-8. doi: 10.1016/j.cellsig.2011.11.020. Epub 2011 Dec 8.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [8] Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma.Drug Des Devel Ther. 2015 Aug 26;9:4897-907.
• [9] Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. Int J Cancer. 2014 Mar 15;134(6):1484-94.
• [10] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [11] Crizotinib for the treatment of non-small-cell lung cancer. Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7.
• [12] Prediction of crizotinib-midazolam interaction using the Simcyp population-based simulator: comparison of CYP3A time-dependent inhibition between human liver microsomes versus hepatocytes. Drug Metab Dispos. 2013 Feb;41(2):343-52.
• [13] Editor's Highlight: PlacentalDisposition and Effects of Crizotinib: An Ex Vivo Study in the Isolated Dual-Side Perfused Human Cotyledon. Toxicol Sci. 2017 Jun 1;157(2):500-509. doi: 10.1093/toxsci/kfx063.
• [14] Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012 Feb 8;4(120):120ra17. doi: 10.1126/scitranslmed.3003316. Epub 2012 Jan 25.
• [15] Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes. Toxicol Appl Pharmacol. 2013 Oct 1;272(1):245-55.
• [16] Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012 Nov 1;118(21):5302-9. doi: 10.1002/cncr.27450. Epub 2012 Apr 4.
• [17] Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem. 2011 Sep 22;54(18):6342-63. doi: 10.1021/jm2007613. Epub 2011 Aug 18.
• [18] ROS-dependent DNA damage contributes to crizotinib-induced hepatotoxicity via the apoptotic pathway. Toxicol Appl Pharmacol. 2019 Nov 15;383:114768. doi: 10.1016/j.taap.2019.114768. Epub 2019 Oct 19.
• [19] Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
• [20] Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
• [21] Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40. doi: 10.1073/pnas.1019559108. Epub 2011 Apr 18.
• [22] Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor resistance in EML4-ALK lung cancer cells. Clin Cancer Res. 2012 Jul 1;18(13):3592-602. doi: 10.1158/1078-0432.CCR-11-2972. Epub 2012 May 2.
• [23] Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen. Chem Biol Drug Des. 2011 Dec;78(6):999-1005. doi: 10.1111/j.1747-0285.2011.01239.x. Epub 2011 Oct 31.
• [24] Tyrosine phosphorylation of the scaffold protein IQGAP1 in the MET pathway alters function. J Biol Chem. 2020 Dec 25;295(52):18105-18121. doi: 10.1074/jbc.RA120.015891. Epub 2020 Oct 21.
• [25] Keratinocytes apoptosis contributes to crizotinib induced-erythroderma. Toxicol Lett. 2020 Feb 1;319:102-110. doi: 10.1016/j.toxlet.2019.11.007. Epub 2019 Nov 7.
• [26] Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012 Mar 1;18(5):1472-82. doi: 10.1158/1078-0432.CCR-11-2906. Epub 2012 Jan 10.
• [27] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [28] Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion. J Biomed Res. 2016 Mar;30(2):120-133.
• [29] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [30] Epirubicin glucuronidation and UGT2B7 developmental expression. Drug Metab Dispos. 2006 Dec;34(12):2097-101.
• [31] Co-encapsulation of chrysophsin-1 and epirubicin in PEGylated liposomes circumvents multidrug resistance in HeLa cells. Chem Biol Interact. 2015 Dec 5;242:13-23. doi: 10.1016/j.cbi.2015.08.023. Epub 2015 Sep 1.
• [32] Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer Res. 1999 Dec 1;59(23):5938-46.
• [33] Preliminary study on behaviour of atrial natriuretic factor in anthracycline-related cardiac toxicity. Int J Clin Pharmacol Res. 1991;11(2):75-81.
• [34] 7,3',4'-Trihydroxyisoflavone modulates multidrug resistance transporters and induces apoptosis via production of reactive oxygen species. Toxicology. 2012 Dec 16;302(2-3):221-32. doi: 10.1016/j.tox.2012.08.003. Epub 2012 Aug 15.
• [35] Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist. 2007 Sep;12(9):1124-33. doi: 10.1634/theoncologist.12-9-1124.
• [36] Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers. Oncologist. 2008 Dec;13(12):1296-305. doi: 10.1634/theoncologist.2008-0151. Epub 2008 Dec 5.
• [37] Evidence for direct involvement of epirubicin in the formation of chromosomal translocations in t(15;17) therapy-related acute promyelocytic leukemia. Blood. 2010 Jan 14;115(2):326-30. doi: 10.1182/blood-2009-07-235051. Epub 2009 Nov 2.
• [38] (-)-Gossypol enhances the anticancer activity of epirubicin via downregulating survivin in hepatocellular carcinoma. Chem Biol Interact. 2022 Sep 1;364:110060. doi: 10.1016/j.cbi.2022.110060. Epub 2022 Jul 22.
• [39] The differential effects of cyclophosphamide, epirubicin and 5-fluorouracil on apoptotic marker (CPP-32), pro-apoptotic protein (p21(WAF-1)) and anti-apoptotic protein (bcl-2) in breast cancer cells. Breast Cancer Res Treat. 2003 Aug;80(3):239-44. doi: 10.1023/A:1024995202135.
• [40] Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.
• [41] MARVELD1 attenuates arsenic trioxide-induced apoptosis in liver cancer cells by inhibiting reactive oxygen species production. Ann Transl Med. 2019 May;7(9):200. doi: 10.21037/atm.2019.04.38.
• [42] Genome-wide association study of epirubicin-induced leukopenia in Japanese patients. Pharmacogenet Genomics. 2011 Sep;21(9):552-8. doi: 10.1097/FPC.0b013e328348e48f.
• [43] [Knock-down of apollon gene by antisense oligodeoxynucleotide inhibits the proliferation of Lovo cells and enhances chemo-sensitivity]. Yao Xue Xue Bao. 2011 Feb;46(2):138-45.
• [44] [Antisense oligonucleotide targeting survivin induces apoptosis of renal clear-cell carcinoma cells and enhances their sensitivity to epirubicin in vitro]. Zhonghua Zhong Liu Za Zhi. 2005 Aug;27(8):468-70.
• [45] Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity. Br J Cancer. 1998 Apr;77(7):1097-102. doi: 10.1038/bjc.1998.182.
• [46] S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. Oncol Rep. 2008 Aug;20(2):325-32.
• [47] TSSC3 overexpression associates with growth inhibition, apoptosis induction and enhances chemotherapeutic effects in human osteosarcoma. Carcinogenesis. 2012 Jan;33(1):30-40. doi: 10.1093/carcin/bgr232. Epub 2011 Oct 21.
• [48] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.