Details of the Drug Combination

General Information of Drug Combination (ID: DCBWDP3)

• Drug Combination Name: Docetaxel + Pemetrexed
• Indication: Non Small Cell Lung Cancer; Status: Phase 1 [1]
• Component Drugs:
  Docetaxel (DMDI269): Small molecular drug
  Pemetrexed (DMMX2E6): Small molecular drug

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	[9]

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	[10]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[11]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[14]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[15]
TAP-like protein (ABCB9)	DT68UV2	ABCB9_HUMAN	Substrate	[16]
Multidrug resistance-associated protein 7 (ABCC10)	DTPS120	MRP7_HUMAN	Substrate	[17]

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	[18]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[19]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[19]

Docetaxel 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 Response To Substance	[20]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[21]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[21]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Degradation	[22]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[23]
RAF proto-oncogene serine/threonine-protein kinase (RAF1)	OT51LSFO	RAF1_HUMAN	Increases Expression	[24]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[25]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[26]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[25]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[27]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[28]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Decreases Expression	[29]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[30]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[24]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[24]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[29]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Expression	[31]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Activity	[22]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Decreases Phosphorylation	[22]
ELL-associated factor 2 (EAF2)	OTSOET5L	EAF2_HUMAN	Decreases Expression	[29]
Small integral membrane protein 14 (SMIM14)	OT47IF19	SIM14_HUMAN	Decreases Expression	[29]
Protein FAM117A (FAM117A)	OT2FBGGV	F117A_HUMAN	Decreases Expression	[29]
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19)	OTTVT4MB	TNR19_HUMAN	Decreases Expression	[29]
Tropomodulin-2 (TMOD2)	OTTTUH2W	TMOD2_HUMAN	Decreases Expression	[29]
Flavin-containing monooxygenase 3 (FMO3)	OT1G2EV3	FMO3_HUMAN	Affects Response To Substance	[32]
Kinesin heavy chain isoform 5A (KIF5A)	OT3ETTI6	KIF5A_HUMAN	Decreases Response To Substance	[33]
Regulator of G-protein signaling 17 (RGS17)	OT5RVUDS	RGS17_HUMAN	Increases Response To Substance	[34]
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B)	OT8KME51	BUB1B_HUMAN	Affects Response To Substance	[35]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[36]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Response To Substance	[37]
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Increases Response To Substance	[38]
Kinesin-like protein KIFC3 (KIFC3)	OTOPD4QO	KIFC3_HUMAN	Decreases Response To Substance	[33]
Regulator of G-protein signaling 10 (RGS10)	OTQ8N1QH	RGS10_HUMAN	Increases Response To Substance	[34]
E3 ubiquitin-protein ligase CHFR (CHFR)	OTRAD2TT	CHFR_HUMAN	Decreases Response To Substance	[39]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Response To Substance	[40]
Kinesin-like protein KIF12 (KIF12)	OTTALNDD	KIF12_HUMAN	Decreases Response To Substance	[33]
Flavin-containing monooxygenase 2 (FMO2)	OTUJUL9S	FMO2_HUMAN	Affects Response To Substance	[32]
Kinesin-like protein KIF14 (KIF14)	OTXHT4JM	KIF14_HUMAN	Decreases Response To Substance	[41]
Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)	OTXNGZCG	MD2L1_HUMAN	Affects Response To Substance	[35]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Affects Response To Substance	[42]
ATP-binding cassette sub-family C member 6 (ABCC6)	OTZT0LKT	MRP6_HUMAN	Affects Response To Substance	[32]

Indication(s) of Pemetrexed

Disease Entry	ICD 11	Status	REF
Central nervous system lymphoma	2B33.5	Approved	[4]
Epithelioid mesothelioma	2F10	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Malignant pleural mesothelioma	2C26.0	Approved	[5]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Sarcomatoid mesothelioma	N.A.	Approved	[4]
Small-cell lung cancer	2C25.Y	Approved	[4]
Lung neoplasm	N.A.	Investigative	[4]

Pemetrexed Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Candida Thymidylate synthase (Candi TMP1)	TTU6BFZ	TYSY_CANAL	Inhibitor	[45]

Pemetrexed Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[10]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[46]
Multidrug resistance-associated protein 5 (ABCC5)	DTYVM24	MRP5_HUMAN	Substrate	[47]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[48]
Folate transporter 1 (SLC19A1)	DTOSN46	S19A1_HUMAN	Substrate	[49]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[50]

Pemetrexed Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Reduced folate transporter (SLC19A1)	OTWB0BTO	S19A1_HUMAN	Increases Response To Substance	[51]
ATP-binding cassette sub-family C member 5 (ABCC5)	OT34G4US	MRP5_HUMAN	Decreases Response To Substance	[52]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[53]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Decreases Expression	[54]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[55]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[56]
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2)	OT1LQSGX	MTDC_HUMAN	Increases Response To Substance	[57]
Splicing factor 45 (RBM17)	OT9ROJCL	SPF45_HUMAN	Decreases Response To Substance	[58]
ATP-binding cassette sub-family C member 11 (ABCC11)	OTVHL7OR	MRP8_HUMAN	Decreases Response To Substance	[59]
Folylpolyglutamate synthase, mitochondrial (FPGS)	OTW3F1ZE	FOLC_HUMAN	Increases Response To Substance	[44]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Response To Substance	[53]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast Cancer	DC4YXHW	N. A.	Phase 1	[60]
Lung Cancer	DC7M6MW	N. A.	Phase 1	[61]

References

• [1] ClinicalTrials.gov (NCT00684099) Docetaxel/Pemetrexed as 1st Line Treatment in Patients With Non Small Cell Lung Cancer (NSCLC)
• [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] Pemetrexed 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: 6837).
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Docetaxel: a review of its use in metastatic breast cancer. Drugs. 2005;65(17):2513-31.
• [10] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] FDA Drug Development and Drug Interactions
• [15] 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.
• [16] 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.
• [17] Modulation of the ATPase and transport activities of broad-acting multidrug resistance factor ABCC10 (MRP7). Cancer Res. 2012 Dec 15;72(24):6457-67.
• [18] 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.
• [19] Drug Interactions Flockhart Table
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] Docetaxel induced cardiotoxicity. Heart. 2001 Aug;86(2):219. doi: 10.1136/heart.86.2.219.
• [29] 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.
• [30] [The mechanism of docetaxel-induced apoptosis in human lung cancer cells]. Zhonghua Zhong Liu Za Zhi. 2000 May;22(3):208-11.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] [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.
• [37] 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.
• [38] 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.
• [39] Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes. Int J Oncol. 2007 Oct;31(4):713-20.
• [40] 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.
• [41] 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.
• [42] 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.
• [43] Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels. Br J Cancer. 2007 Mar 12;96(5):769-75.
• [44] A randomized, double-blind, phase II study of two doses of pemetrexed as first-line chemotherapy for advanced breast cancer. Clin Cancer Res. 2007 Jun 15;13(12):3652-9. doi: 10.1158/1078-0432.CCR-06-2377.
• [45] Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer. 2009 Mar;10 Suppl 1:S35-40.
• [46] pH-Dependent transport of pemetrexed by breast cancer resistance protein. Drug Metab Dispos. 2011 Sep;39(9):1478-85.
• [47] Kinetic validation of the use of carboxydichlorofluorescein as a drug surrogate for MRP5-mediated transport. Eur J Pharm Sci. 2006 Apr;27(5):524-32.
• [48] Substrate- and pH-specific antifolate transport mediated by organic anion-transporting polypeptide 2B1 (OATP2B1-SLCO2B1). Mol Pharmacol. 2012 Feb;81(2):134-42.
• [49] Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr. 2014;73:175-204.
• [50] The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol Pharmacol. 2008 Sep;74(3):854-62.
• [51] The inverse relationship between reduced folate carrier function and pemetrexed activity in a human colon cancer cell line. Mol Cancer Ther. 2006 Feb;5(2):438-49. doi: 10.1158/1535-7163.MCT-05-0243.
• [52] The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol Cancer Ther. 2005 May;4(5):855-63.
• [53] Death receptor 5 and cellular FLICE-inhibitory protein regulate pemetrexed-induced apoptosis in human lung cancer cells. Eur J Cancer. 2011 Nov;47(16):2471-8. doi: 10.1016/j.ejca.2011.06.003. Epub 2011 Jul 2.
• [54] Pemetrexed downregulates ERCC1 expression and enhances cytotoxicity effected by resveratrol in human nonsmall cell lung cancer cells. Naunyn Schmiedebergs Arch Pharmacol. 2013 Dec;386(12):1047-59. doi: 10.1007/s00210-013-0905-9. Epub 2013 Aug 3.
• [55] The roles of thymidylate synthase and p53 in regulating Fas-mediated apoptosis in response to antimetabolites. Clin Cancer Res. 2004 May 15;10(10):3562-71. doi: 10.1158/1078-0432.CCR-03-0532.
• [56] Xanthohumol inhibits non-small cell lung cancer by activating PUMA-mediated apoptosis. Toxicology. 2022 Mar 30;470:153141. doi: 10.1016/j.tox.2022.153141. Epub 2022 Mar 5.
• [57] KRAS mutation status is associated with enhanced dependency on folate metabolism pathways in non-small cell lung cancer cells. Mol Cancer Ther. 2014 Jun;13(6):1611-24. doi: 10.1158/1535-7163.MCT-13-0649. Epub 2014 Mar 31.
• [58] Human splicing factor SPF45 (RBM17) confers broad multidrug resistance to anticancer drugs when overexpressed--a phenotype partially reversed by selective estrogen receptor modulators. Cancer Res. 2005 Aug 1;65(15):6593-600. doi: 10.1158/0008-5472.CAN-03-3675.
• [59] ABCC11/MRP8 confers pemetrexed resistance in lung cancer. Cancer Sci. 2010 Nov;101(11):2404-10.
• [60] ClinicalTrials.gov (NCT01172028) Pemetrexed Disodium and Docetaxel in Treating Patients With Advanced Solid Tumors
• [61] ClinicalTrials.gov (NCT00660816) Pemetrexed or Docetaxel With or Without Erlotinib in Stage IIIB or Stage IV Non-Small Cell Lung Cancer