Details of the Drug Combination

General Information of Drug Combination (ID: DCKJSSN)

• Drug Combination Name: Docetaxel + Hydroxychloroquine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Docetaxel (DMDI269): Small molecular drug
  Hydroxychloroquine (DMSIVND): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 2.37
  Bliss Independence Score: 2.37
  Loewe Additivity Score: 2.82
  LHighest Single Agent (HSA) Score: 2.82

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Docetaxel

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[2]
Breast carcinoma	N.A.	Approved	[2]
Head and neck cancer	2D42	Approved	[2]
Leiomyosarcoma	2B58	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[2]
Prostate adenocarcinoma	N.A.	Approved	[2]
Prostate cancer	2C82.0	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Urinary system neoplasm	N.A.	Approved	[2]
Gastric cancer	2B72	Investigative	[2]

Docetaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[10]

Docetaxel Interacts with 8 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[11]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[12]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[14]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[15]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[16]
TAP-like protein (ABCB9)	DT68UV2	ABCB9_HUMAN	Substrate	[17]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[18]

Docetaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[19]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[20]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[20]

Docetaxel Interacts with 83 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Response To Substance	[21]
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases ADR	[22]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[23]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Response To Substance	[21]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[24]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[25]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[26]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[26]
Progesterone receptor (PGR)	OT0FZ3QE	PRGR_HUMAN	Decreases Expression	[26]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Expression	[26]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[26]
Dihydropyrimidine dehydrogenase (DPYD)	OTWRF2NR	DPYD_HUMAN	Decreases Activity	[7]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[27]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[27]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Degradation	[28]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[29]
PC4 and SFRS1-interacting protein (PSIP1)	OT4YAFUS	PSIP1_HUMAN	Increases Cleavage	[30]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Increases Expression	[31]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases Secretion	[32]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[8]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[33]
Protein kinase C beta type (PRKCB)	OTYQ0656	KPCB_HUMAN	Increases Phosphorylation	[34]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[35]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Increases Activity	[36]
Prostate-specific antigen (KLK3)	OTFGSBFJ	KLK3_HUMAN	Decreases Expression	[37]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[33]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Expression	[38]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[39]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[40]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Decreases Expression	[41]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Decreases Expression	[41]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Activity	[36]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[42]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[31]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[31]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Phosphorylation	[9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[41]
Signal transducer and activator of transcription 3 (STAT3)	OTAAGKYZ	STAT3_HUMAN	Decreases Phosphorylation	[43]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[30]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[44]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[24]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[45]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[46]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Increases Expression	[8]
Focal adhesion kinase 1 (PTK2)	OT3Q1JDY	FAK1_HUMAN	Increases Cleavage	[47]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[48]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Increases Expression	[28]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[47]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Activity	[28]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Phosphorylation	[28]
ELL-associated factor 2 (EAF2)	OTSOET5L	EAF2_HUMAN	Decreases Expression	[41]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[41]
Protein FAM117A (FAM117A)	OT2FBGGV	F117A_HUMAN	Decreases Expression	[41]
Delta-like protein 4 (DLL4)	OTRA4K2V	DLL4_HUMAN	Increases Expression	[45]
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19)	OTTVT4MB	TNR19_HUMAN	Decreases Expression	[41]
Tropomodulin-2 (TMOD2)	OTTTUH2W	TMOD2_HUMAN	Decreases Expression	[41]
Flavin-containing monooxygenase 3 (FMO3)	OT1G2EV3	FMO3_HUMAN	Affects Response To Substance	[49]
Kinesin heavy chain isoform 5A (KIF5A)	OT3ETTI6	KIF5A_HUMAN	Decreases Response To Substance	[50]
Proteinase-activated receptor 1 (F2R)	OT4WVWBO	PAR1_HUMAN	Decreases Response To Substance	[51]
ATP-binding cassette sub-family G member 1 (ABCG1)	OT5BG6MK	ABCG1_HUMAN	Affects Response To Substance	[49]
Regulator of G-protein signaling 17 (RGS17)	OT5RVUDS	RGS17_HUMAN	Increases Response To Substance	[52]
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B)	OT8KME51	BUB1B_HUMAN	Affects Response To Substance	[53]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Response To Substance	[54]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[55]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Response To Substance	[56]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Affects Response To Substance	[49]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Response To Substance	[21]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Response To Substance	[57]
Kinesin-like protein KIFC3 (KIFC3)	OTOPD4QO	KIFC3_HUMAN	Decreases Response To Substance	[50]
Regulator of G-protein signaling 10 (RGS10)	OTQ8N1QH	RGS10_HUMAN	Increases Response To Substance	[52]
E3 ubiquitin-protein ligase CHFR (CHFR)	OTRAD2TT	CHFR_HUMAN	Decreases Response To Substance	[58]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Response To Substance	[59]
Cell surface glycoprotein MUC18 (MCAM)	OTT8XKGE	MUC18_HUMAN	Decreases Response To Substance	[60]
Kinesin-like protein KIF12 (KIF12)	OTTALNDD	KIF12_HUMAN	Decreases Response To Substance	[50]
Nucleophosmin (NPM1)	OTTBYYT0	NPM_HUMAN	Decreases Response To Substance	[61]
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Affects Response To Substance	[49]
NADPH--cytochrome P450 reductase (POR)	OTVIDOCH	NCPR_HUMAN	Increases Response To Substance	[21]
Kinesin-like protein KIF14 (KIF14)	OTXHT4JM	KIF14_HUMAN	Decreases Response To Substance	[62]
Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)	OTXNGZCG	MD2L1_HUMAN	Affects Response To Substance	[53]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Affects Response To Substance	[63]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Affects Response To Substance	[64]
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Response To Substance	[49]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Affects Response To Substance	[49]

Indication(s) of Hydroxychloroquine

Disease Entry	ICD 11	Status	REF
Chronic renal failure	GB61.Z	Approved	[4]
Malaria	1F40-1F45	Approved	[5]
Plasmodium falciparum malaria	1F40	Approved	[4]
Plasmodium malariae malaria	N.A.	Approved	[4]
Plasmodium ovale malaria	N.A.	Approved	[4]
Systemic lupus erythematosus	4A40.0	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Colon cancer	2B90.Z	Investigative	[4]

Hydroxychloroquine Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HUMAN pH-dependent viral fusion/replication (pH-DVF/R)	TTD16BI	N.A.	Inhibitor	[65]
HUMAN glycosylation of host receptor (GHR)	TTZGK1R	N.A.	Inhibitor	[65]
Toll-like receptor 7 (TLR7)	TTRJ1K4	TLR7_HUMAN	Antagonist	[66]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway)	TT3A1EZ	N.A.	Inhibitor	[67]

Hydroxychloroquine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[68]

Hydroxychloroquine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[69]

Hydroxychloroquine Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[70]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Increases Expression	[71]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[72]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[71]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)	OT4TMERS	NFAC1_HUMAN	Affects Expression	[73]
Claudin-1 (CLDN1)	OT27KV99	CLD1_HUMAN	Increases Expression	[74]
Interferon beta (IFNB1)	OTYQGUB5	IFNB_HUMAN	Increases Expression	[71]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Increases Expression	[71]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Affects Expression	[75]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Affects Expression	[75]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[71]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Affects Localization	[76]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[77]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[78]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[78]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Degradation	[71]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[73]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[72]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Expression	[71]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Activity	[76]
TNF receptor-associated factor 3 (TRAF3)	OT5TQBGV	TRAF3_HUMAN	Increases Expression	[71]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2)	OTK5T6HZ	NFAC2_HUMAN	Affects Localization	[73]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[79]
Interferon regulatory factor 3 (IRF3)	OT81U8ME	IRF3_HUMAN	Increases Phosphorylation	[71]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Increases Expression	[74]
Mitochondrial antiviral-signaling protein (MAVS)	OTTQ0J64	MAVS_HUMAN	Increases Expression	[71]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Increases Expression	[71]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Increases Expression	[71]
Toll-like receptor 9 (TLR9)	OTFZ45HX	TLR9_HUMAN	Decreases Expression	[80]
7-dehydrocholesterol reductase (DHCR7)	OTLILBUI	DHCR7_HUMAN	Affects Expression	[75]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Prostate Cancer	DCPKO3J	N. A.	Phase 1	[81]

References

• [1] 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.
• [2] Docetaxel FDA Label
• [3] 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: 6809).
• [4] Hydroxychloroquine FDA Label
• [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: 7198).
• [6] ClinicalTrials.gov (NCT04341727) Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352). U.S. National Institutes of Health.
• [7] Synergistic effects of docetaxel and S-1 by modulating the expression of metabolic enzymes of 5-fluorouracil in human gastric cancer cell lines. Int J Cancer. 2006 Aug 15;119(4):783-91.
• [8] Induction of tubulin by docetaxel is associated with p53 status in human non small cell lung cancer cell lines. Int J Cancer. 2006 Jan 15;118(2):317-25. doi: 10.1002/ijc.21372.
• [9] Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cells. Int J Cancer. 2005 Jun 20;115(3):484-92. doi: 10.1002/ijc.20878.
• [10] Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513-31.
• [11] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [12] Transport of diclofenac by breast cancer resistance protein (ABCG2) and stimulation of multidrug resistance protein 2 (ABCC2)-mediated drug transport by diclofenac and benzbromarone. Drug Metab Dispos. 2009 Jan;37(1):129-36.
• [13] Effect of ABCB1 C3435T polymorphism on docetaxel pharmacokinetics according to menopausal status in breast cancer patients. Br J Cancer. 2010 Aug 10;103(4):560-6.
• [14] Ixabepilone, a novel microtubule-targeting agent for breast cancer, is a substrate for P-glycoprotein (P-gp/MDR1/ABCB1) but not breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2011 May;337(2):423-32.
• [15] FDA Drug Development and Drug Interactions
• [16] Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes. Cancer Lett. 2008 Feb 18;260(1-2):163-9.
• [17] RNA-sequencing dissects the transcriptome of polyploid cancer cells that are resistant to combined treatments of cisplatin with paclitaxel and docetaxel. Mol Biosyst. 2017 Sep 26;13(10):2125-2134.
• [18] Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7). Cancer Res. 2012 Dec 15;72(24):6457-67.
• [19] Randomized pharmacokinetic and pharmacodynamic study of docetaxel: dosing based on body-surface area compared with individualized dosing based on cytochrome P450 activity estimated using a urinary metabolite of exogenous cortisol. J Clin Oncol. 2005 Feb 20;23(6):1061-9.
• [20] Drug Interactions Flockhart Table
• [21] Concise prediction models of anticancer efficacy of 8 drugs using expression data from 12 selected genes. Int J Cancer. 2004 Sep 10;111(4):617-26. doi: 10.1002/ijc.20289.
• [22] Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia. Cancer Sci. 2008 May;99(5):967-72.
• [23] 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.
• [24] Enhanced chemotherapeutic efficacy of docetaxel in human lung cancer cell line via GLUT1 inhibitor. J Biochem Mol Toxicol. 2023 Jun;37(6):e23348. doi: 10.1002/jbt.23348. Epub 2023 Mar 31.
• [25] Comparison of burst of reactive oxygen species and activation of caspase-3 in apoptosis of K562 and HL-60 cells induced by docetaxel. Cancer Lett. 2004 Oct 8;214(1):103-13. doi: 10.1016/j.canlet.2004.03.047.
• [26] Down-regulation of intratumoral aromatase messenger RNA levels by docetaxel in human breast cancers. Clin Cancer Res. 2004 Dec 15;10(24):8163-9.
• [27] Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels. Cancer Res. 2001 Jan 15;61(2):759-63.
• [28] Docetaxel-induced apoptosis of human melanoma is mediated by activation of c-Jun NH2-terminal kinase and inhibited by the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway. Clin Cancer Res. 2007 Feb 15;13(4):1308-14. doi: 10.1158/1078-0432.CCR-06-2216.
• [29] PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer Chemother Pharmacol. 2010 Sep;66(4):765-71. doi: 10.1007/s00280-009-1221-4. Epub 2009 Dec 30.
• [30] Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75. Mol Cancer. 2009 Aug 28;8:68. doi: 10.1186/1476-4598-8-68.
• [31] Docetaxel induces p53-dependent apoptosis and synergizes with farnesyl transferase inhibitor r115777 in human epithelial cancer cells. Front Biosci. 2005 Sep 1;10:2566-75. doi: 10.2741/1720.
• [32] Kaempferol and quercetin stimulate granulocyte-macrophage colony-stimulating factor secretion in human prostate cancer cells. Mol Cell Endocrinol. 2008 Jun 11;287(1-2):57-64. doi: 10.1016/j.mce.2008.01.015. Epub 2008 Feb 3.
• [33] All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells. Oncogene. 2004 Jan 15;23(2):426-33. doi: 10.1038/sj.onc.1207040.
• [34] Docetaxel Facilitates Endothelial Dysfunction through Oxidative Stress via Modulation of Protein Kinase C Beta: The Protective Effects of Sotrastaurin. Toxicol Sci. 2015 May;145(1):59-67. doi: 10.1093/toxsci/kfv017. Epub 2015 Jan 28.
• [35] Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
• [36] The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther. 2004 Jan;3(1):59-70.
• [37] Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer. Cancer Res. 2010 Oct 15;70(20):7992-8002. doi: 10.1158/0008-5472.CAN-10-0585. Epub 2010 Aug 31.
• [38] Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer. Biochem Pharmacol. 2011 Nov 1;82(9):1100-9. doi: 10.1016/j.bcp.2011.07.078. Epub 2011 Jul 23.
• [39] Replication-dependent -H2AX formation is involved in docetaxel-induced apoptosis in NSCLC A549 cells. Oncol Rep. 2010 Nov;24(5):1297-305. doi: 10.3892/or_00000986.
• [40] Docetaxel induced cardiotoxicity. Heart. 2001 Aug;86(2):219. doi: 10.1136/heart.86.2.219.
• [41] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [42] [The mechanism of docetaxel-induced apoptosis in human lung cancer cells]. Zhonghua Zhong Liu Za Zhi. 2000 May;22(3):208-11.
• [43] Sensitization to docetaxel in prostate cancer cells by green tea and quercetin. J Nutr Biochem. 2015 Apr;26(4):408-15. doi: 10.1016/j.jnutbio.2014.11.017. Epub 2015 Jan 15.
• [44] Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
• [45] Role of delta-like ligand-4 in chemoresistance against docetaxel in MCF-7 cells. Hum Exp Toxicol. 2017 Apr;36(4):328-338. doi: 10.1177/0960327116650006. Epub 2016 Jun 22.
• [46] Roles of CYP3A4, CYP3A5 and CYP2C8 drug-metabolizing enzymes in cellular cytostatic resistance. Chem Biol Interact. 2021 May 1;340:109448. doi: 10.1016/j.cbi.2021.109448. Epub 2021 Mar 26.
• [47] Focal adhesion kinase silencing augments docetaxel-mediated apoptosis in ovarian cancer cells. Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8829-36. doi: 10.1158/1078-0432.CCR-05-1728.
• [48] Enhanced Bax in oral SCC in relation to antitumor effects of chemotherapy. J Oral Pathol Med. 2005 Feb;34(2):93-9. doi: 10.1111/j.1600-0714.2004.00257.x.
• [49] Pharmacogenomics variation in drug metabolizing enzymes and transporters in relation to docetaxel toxicity in Lebanese breast cancer patients: paving the way for OMICs in low and middle income countries. OMICS. 2013 Jul;17(7):353-67. doi: 10.1089/omi.2013.0019. Epub 2013 Jun 11.
• [50] Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer. Breast Cancer Res Treat. 2012 Feb;131(3):849-58. doi: 10.1007/s10549-011-1500-8. Epub 2011 Apr 9.
• [51] PAR1-mediated NFkappaB activation promotes survival of prostate cancer cells through a Bcl-xL-dependent mechanism. J Cell Biochem. 2005 Oct 15;96(3):641-52. doi: 10.1002/jcb.20533.
• [52] Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer. 2010 Nov 2;9:289. doi: 10.1186/1476-4598-9-289.
• [53] Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy. Clin Oncol (R Coll Radiol). 2008 Oct;20(8):639-46. doi: 10.1016/j.clon.2008.06.010. Epub 2008 Aug 8.
• [54] EGFR mediates docetaxel resistance in human castration-resistant prostate cancer through the Akt-dependent expression of ABCB1 (MDR1). Arch Toxicol. 2015 Apr;89(4):591-605. doi: 10.1007/s00204-014-1275-x. Epub 2014 Jun 3.
• [55] [Antisense RNA targeting survivin enhances the chemosensitivity of LOVO/Adr cells to taxotere]. Zhonghua Wei Chang Wai Ke Za Zhi. 2005 Sep;8(5):455-8.
• [56] Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma. Antioxid Redox Signal. 2014 May 20;20(15):2326-46. doi: 10.1089/ars.2013.5295. Epub 2013 Nov 14.
• [57] HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel. Breast Cancer Res Treat. 2004 Aug;86(3):197-206. doi: 10.1023/B:BREA.0000036783.88387.47.
• [58] Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes. Int J Oncol. 2007 Oct;31(4):713-20.
• [59] Differential effect of anti-apoptotic genes Bcl-xL and c-FLIP on sensitivity of MCF-7 breast cancer cells to paclitaxel and docetaxel. Anticancer Res. 2005 May-Jun;25(3c):2367-79.
• [60] CD146 expression in human breast cancer cell lines induces phenotypic and functional changes observed in Epithelial to Mesenchymal Transition. PLoS One. 2012;7(8):e43752. doi: 10.1371/journal.pone.0043752. Epub 2012 Aug 30.
• [61] Proteomic identification of differentially expressed proteins associated with the multiple drug resistance in methotrexate-resistant human breast cancer cells. Int J Oncol. 2014 Jul;45(1):448-58.
• [62] KIF14 promotes AKT phosphorylation and contributes to chemoresistance in triple-negative breast cancer. Neoplasia. 2014 Mar;16(3):247-56, 256.e2. doi: 10.1016/j.neo.2014.03.008.
• [63] The prognostic gene CRABP2 affects drug sensitivity by regulating docetaxel-induced apoptosis in breast invasive carcinoma: A pan-cancer analysis. Chem Biol Interact. 2023 Mar 1;373:110372. doi: 10.1016/j.cbi.2023.110372. Epub 2023 Feb 2.
• [64] Association of the CYP1B1*3 allele with survival in patients with prostate cancer receiving docetaxel. Mol Cancer Ther. 2008 Jan;7(1):19-26. doi: 10.1158/1535-7163.MCT-07-0557. Epub 2008 Jan 9.
• [65] Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
• [66] TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
• [67] Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166.
• [68] MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
• [69] Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
• [70] Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M "Influence of hydroxychloroquine on the bioavailability of oral metoprolol." Br J Clin Pharmacol 49 (2000): 549-54. [PMID: 10848718]
• [71] Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
• [72] Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. Clin Exp Immunol. 2006 Jun;144(3):503-11. doi: 10.1111/j.1365-2249.2006.03070.x.
• [73] Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.
• [74] Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
• [75] Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
• [76] Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene. 2003 Jun 19;22(25):3927-36. doi: 10.1038/sj.onc.1206622.
• [77] Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression. Environ Toxicol. 2021 Nov;36(11):2138-2145. doi: 10.1002/tox.23328. Epub 2021 Jul 19.
• [78] Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. Glia. 2004 Jul;47(1):9-20. doi: 10.1002/glia.20017.
• [79] d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions. Toxicol Lett. 2018 Jun 1;289:99-106. doi: 10.1016/j.toxlet.2018.02.001. Epub 2018 Feb 6.
• [80] Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther. 2012 Apr 18;14(2):R80. doi: 10.1186/ar3803.
• [81] ClinicalTrials.gov (NCT00786682) Docetaxel and Hydroxychloroquine in Treating Patients With Metastatic Prostate Cancer