Details of the Drug Combination

General Information of Drug Combination (ID: DCVGO4J)

• Drug Combination Name: Romidepsin + Chlorambucil
• Indication: Lung adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Romidepsin (DMT5GNL): Small molecular drug
  Chlorambucil (DMRKE63): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MDA-MB-231
  Zero Interaction Potency (ZIP) Score: 7.15
  Bliss Independence Score: 7.66
  Loewe Additivity Score: 5.39
  LHighest Single Agent (HSA) Score: 6.98

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Romidepsin

Disease Entry	ICD 11	Status	REF
Cutaneous T-cell lymphoma	2B01	Approved	[2]
Gastrin-producing neuroendocrine tumor	N.A.	Approved	[3]
Glucagonoma	N.A.	Approved	[3]
Insulinoma	2C10.1	Approved	[3]
Lung carcinoid tumor	N.A.	Approved	[3]
Melanoma	2C30	Approved	[3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[3]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[3]
Urethral cancer	2C93	Approved	[3]
Peripheral T-cell lymphoma	2A90.C	Phase 3	[4]
Renal cell carcinoma	2C90	Phase 3	[2]

Romidepsin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histone deacetylase 1 (HDAC1)	TT6R7JZ	HDAC1_HUMAN	Inhibitor	[9]

Romidepsin Interacts with 2 DTP Molecule(s)

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

Romidepsin Interacts with 3 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	[12]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[13]

Romidepsin Interacts with 41 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[14]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Expression	[15]
E3 SUMO-protein ligase CBX4 (CBX4)	OT4XVRRF	CBX4_HUMAN	Increases Expression	[16]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[17]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[18]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)	OTL9I7LO	GA45B_HUMAN	Increases Expression	[19]
Serine/threonine-protein kinase 17B (STK17B)	OT4NYNO8	ST17B_HUMAN	Increases Expression	[16]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Expression	[20]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Decreases Expression	[20]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[20]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Phosphorylation	[20]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[21]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Increases Expression	[16]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[20]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[8]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[16]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Expression	[21]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[20]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[8]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[8]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[22]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Decreases Phosphorylation	[8]
Sterol regulatory element-binding protein 1 (SREBF1)	OTWBRPAI	SRBP1_HUMAN	Increases Expression	[16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[23]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[20]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[21]
Friend leukemia integration 1 transcription factor (FLI1)	OT0EV3LX	FLI1_HUMAN	Decreases Expression	[24]
RNA-binding protein EWS (EWSR1)	OT7SRHV3	EWS_HUMAN	Decreases Expression	[24]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[8]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[22]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[16]
Spectrin alpha chain, non-erythrocytic 1 (SPTAN1)	OT6VY3A3	SPTN1_HUMAN	Increases Expression	[16]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Increases Expression	[25]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[22]
Histone H3.1t (H3-4)	OTY6ITYF	H31T_HUMAN	Increases Acetylation	[25]
Sodium/iodide cotransporter (SLC5A5)	OTU7E9G7	SC5A5_HUMAN	Increases Expression	[26]
Mitogen-activated protein kinase kinase kinase 3 (MAP3K3)	OT53LJGW	M3K3_HUMAN	Increases Expression	[16]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Affects Metabolism	[27]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[28]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Decreases Response To Substance	[21]

Indication(s) of Chlorambucil

Disease Entry	ICD 11	Status	REF
Chronic lymphocytic leukaemia	2A82.0	Approved	[5]
Small lymphocytic lymphoma	2A82.0	Approved	[6]
Classic Hodgkin lymphoma	N.A.	Investigative	[6]
Follicular lymphoma	2A80	Investigative	[6]

Chlorambucil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA replication (DNA repli)	TTABD5E	NOUNIPROTAC	Intercalator	[29]

Chlorambucil Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[30]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[31]

Chlorambucil Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[32]

Chlorambucil Interacts with 37 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Response To Substance	[33]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[34]
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Decreases Activity	[35]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Decreases Expression	[36]
Leukemia inhibitory factor (LIF)	OTO46S5S	LIF_HUMAN	Increases Expression	[36]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Expression	[36]
Bcl-2-interacting killer (BIK)	OTTH1T3D	BIK_HUMAN	Increases Expression	[36]
F-box only protein 30 (FBXO30)	OTD1P6LA	FBX30_HUMAN	Decreases Expression	[36]
Histone chaperone ASF1A (ASF1A)	OT4S44GP	ASF1A_HUMAN	Decreases Expression	[36]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Affects Expression	[37]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[38]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Affects Expression	[39]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Increases Expression	[40]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[38]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[40]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Phosphorylation	[41]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Affects Expression	[42]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[43]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[38]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[44]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[43]
Histone H4 (H4C1)	OTB71W46	H4_HUMAN	Decreases Expression	[41]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[39]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Increases Expression	[45]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[46]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[43]
kinase isozyme 4, mitochondrial (PDK4)	OTCMHMBZ	PDK4_HUMAN	Affects Expression	[47]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[39]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Response To Substance	[48]
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Response To Substance	[49]
Cytidine deaminase (CDA)	OT3HXP6N	CDD_HUMAN	Decreases Response To Substance	[50]
Fanconi anemia group G protein (FANCG)	OT7MC8TZ	FANCG_HUMAN	Increases Response To Substance	[51]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Response To Substance	[52]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[33]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Affects Export	[53]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Decreases Response To Substance	[54]
Fanconi anemia group C protein (FANCC)	OTTIDM3P	FANCC_HUMAN	Increases Response To Substance	[51]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast adenocarcinoma	DC8L3IB	MDA-MB-468	Investigative	[55]
Invasive ductal carcinoma	DCS1L2E	HS 578T	Investigative	[55]
Invasive ductal carcinoma	DCI8JXC	T-47D	Investigative	[55]
Cutaneous melanoma	DCTEUYO	SK-MEL-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC7E1JH	OVCAR-8	Investigative	[1]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [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: 7006).
• [3] Romidepsin FDA Label
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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: 7143).
• [6] Chlorambucil FDA Label
• [7] Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin. Fertil Steril. 2011 Apr;95(5):1579-83. doi: 10.1016/j.fertnstert.2010.12.058. Epub 2011 Feb 4.
• [8] Inhibitors of class I HDACs and of FLT3 combine synergistically against leukemia cells with mutant FLT3. Arch Toxicol. 2022 Jan;96(1):177-193. doi: 10.1007/s00204-021-03174-1. Epub 2021 Oct 19.
• [9] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [10] Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503.
• [11] A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03. Neuro Oncol. 2011 May;13(5):509-16.
• [12] Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res. 2009 Feb 15;15(4):1496-503.
• [13] FDA Label of Romidepsin. The 2020 official website of the U.S. Food and Drug Administration.
• [14] Chemoresistance to depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is mediated by reversible MDR1 induction in human cancer cell lines. J Pharmacol Exp Ther. 2005 Jul;314(1):467-75. doi: 10.1124/jpet.105.083956. Epub 2005 Apr 15.
• [15] Aberrant promoter methylation of the ABCG2 gene in renal carcinoma. Mol Cell Biol. 2006 Nov;26(22):8572-85.
• [16] 5-Aza-2'-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer). Biochem Biophys Res Commun. 2006 Dec 15;351(2):455-61. doi: 10.1016/j.bbrc.2006.10.055. Epub 2006 Oct 18.
• [17] Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity. Cancer Res. 2006 Jul 15;66(14):7317-25. doi: 10.1158/0008-5472.CAN-06-0680.
• [18] Histone deacetylase inhibitors FK228, N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)amino- methyl]benzamide and m-carboxycinnamic acid bis-hydroxamide augment radiation-induced cell death in gastrointestinal adenocarcinoma cells. Int J Cancer. 2004 Jun 10;110(2):301-8. doi: 10.1002/ijc.20117.
• [19] A sequential treatment of depsipeptide followed by 5-azacytidine enhances Gadd45beta expression in hepatocellular carcinoma cells. Anticancer Res. 2007 Nov-Dec;27(6B):3783-9.
• [20] Abrogation of p21 expression by flavopiridol enhances depsipeptide-mediated apoptosis in malignant pleural mesothelioma cells. Clin Cancer Res. 2004 Mar 1;10(5):1813-25. doi: 10.1158/1078-0432.ccr-0901-3.
• [21] Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells. Clin Cancer Res. 2008 Jan 15;14(2):549-58. doi: 10.1158/1078-0432.CCR-07-1934.
• [22] Blocking downstream signaling pathways in the context of HDAC inhibition promotes apoptosis preferentially in cells harboring mutant Ras. Oncotarget. 2016 Oct 25;7(43):69804-69815. doi: 10.18632/oncotarget.12001.
• [23] Up-regulation of MDR1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (FK228) and ATRA in acute promyelocytic leukemia cells. Blood. 2006 Feb 15;107(4):1546-54. doi: 10.1182/blood-2004-10-4126. Epub 2005 Oct 13.
• [24] Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors. Int J Cancer. 2005 Sep 20;116(5):784-92. doi: 10.1002/ijc.21069.
• [25] Enhanced transgene expression in urothelial cancer gene therapy with histone deacetylase inhibitor. J Urol. 2005 Aug;174(2):747-52. doi: 10.1097/01.ju.0000164723.20555.e6.
• [26] Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer. 2006 Sep;13(3):797-826. doi: 10.1677/erc.1.01143.
• [27] Identification of cytochrome P450 enzymes involved in the metabolism of FK228, a potent histone deacetylase inhibitor, in human liver microsomes. Biol Pharm Bull. 2005 Jan;28(1):124-9.
• [28] Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing's sarcoma cells. Int J Cancer. 2006 Jan 1;118(1):90-7. doi: 10.1002/ijc.21297.
• [29] Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A. Mol Cancer Ther. 2009 Jun;8(6):1714-23.
• [30] 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.
• [31] Transporters and renal drug elimination. Annu Rev Pharmacol Toxicol. 2004;44:137-66.
• [32] The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol. 2008 Jun 27;380(1):131-44.
• [33] The influence of coordinate overexpression of glutathione phase II detoxification gene products on drug resistance. J Pharmacol Exp Ther. 2000 Aug;294(2):480-7.
• [34] Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
• [35] Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistanceKinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity. J Biol Chem. 2001 Mar 16;276(11):7952-6.
• [36] Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
• [37] Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene. 2003 Nov 13;22(51):8356-69. doi: 10.1038/sj.onc.1207004.
• [38] Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells. J Cell Biochem. 2008 May 15;104(2):595-605. doi: 10.1002/jcb.21649.
• [39] Differential gene expression induction by TRAIL in B chronic lymphocytic leukemia (B-CLL) cells showing high versus low levels of Zap-70. J Cell Physiol. 2007 Oct;213(1):229-36. doi: 10.1002/jcp.21116.
• [40] Theophylline synergizes with chlorambucil in inducing apoptosis of B-chronic lymphocytic leukemia cells. Blood. 1996 Sep 15;88(6):2172-82.
• [41] A two-hit mechanism for pre-mitotic arrest of cancer cell proliferation by a polyamide-alkylator conjugate. Cell Cycle. 2006 Jul;5(14):1537-48. doi: 10.4161/cc.5.14.2913. Epub 2006 Jul 17.
• [42] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [43] Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
• [44] Disruption of gene expression and induction of apoptosis in prostate cancer cells by a DNA-damaging agent tethered to an androgen receptor ligand. Chem Biol. 2005 Jul;12(7):779-87. doi: 10.1016/j.chembiol.2005.05.009.
• [45] Chlorambucil induction of HsRad51 in B-cell chronic lymphocytic leukemia. Clin Cancer Res. 1999 Aug;5(8):2178-84.
• [46] Bcl-2 antisense oligonucleotides enhance the cytotoxicity of chlorambucil in B-cell chronic lymphocytic leukaemia cells. Leuk Lymphoma. 2001 Jul;42(3):491-8. doi: 10.3109/10428190109064606.
• [47] The MT1G Gene in LUHMES Neurons Is a Sensitive Biomarker of Neurotoxicity. Neurotox Res. 2020 Dec;38(4):967-978. doi: 10.1007/s12640-020-00272-3. Epub 2020 Sep 1.
• [48] Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis. 2009 Sep;30(9):1571-80. doi: 10.1093/carcin/bgp176. Epub 2009 Jul 16.
• [49] Increased resistance to nitrogen mustards and antifolates following in vitro selection of murine fibroblasts and primary hematopoietic cells transduced with a bicistronic retroviral vector expressing the rat glutathione S-transferase A3 and a mutant dihydrofolate reductase. Cancer Gene Ther. 2003 Aug;10(8):637-46. doi: 10.1038/sj.cgt.7700619.
• [50] Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicistronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts. Cancer Gene Ther. 2000 May;7(5):757-65. doi: 10.1038/sj.cgt.7700169.
• [51] In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor. Clin Cancer Res. 2005 Oct 15;11(20):7508-15. doi: 10.1158/1078-0432.CCR-05-1048.
• [52] Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000 May;6(5):1796-803.
• [53] Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated resistance to chlorambucil cytotoxicity. J Pharmacol Exp Ther. 2004 Jan;308(1):260-7. doi: 10.1124/jpet.103.057729. Epub 2003 Oct 20.
• [54] Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects. Mol Pharmacol. 2004 Apr;65(4):897-905. doi: 10.1124/mol.65.4.897.
• [55] 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.