Details of the Drug Combination

General Information of Drug Combination (ID: DCJFMX0)

Drug Combination Name
Docetaxel GDC-0032
Indication
Disease Entry Status REF
Breast Cancer, Non-small Lung Cancer Phase 1 [1]
Component Drugs Docetaxel   DMDI269 GDC-0032   DMT4QHD
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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]
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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]
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⏷ Show the Full List of 8 DTP(s)
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]
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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 [20]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases ADR [21]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Increases Expression [22]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Response To Substance [20]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [23]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [24]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Expression [25]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [25]
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Decreases Expression [25]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Expression [25]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Increases Expression [25]
Dihydropyrimidine dehydrogenase (DPYD) OTWRF2NR DPYD_HUMAN Decreases Activity [6]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Increases Expression [26]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Increases Expression [26]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Degradation [27]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [28]
PC4 and SFRS1-interacting protein (PSIP1) OT4YAFUS PSIP1_HUMAN Increases Cleavage [29]
RAF proto-oncogene serine/threonine-protein kinase (RAF1) OT51LSFO RAF1_HUMAN Increases Expression [30]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases Secretion [31]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [7]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [32]
Protein kinase C beta type (PRKCB) OTYQ0656 KPCB_HUMAN Increases Phosphorylation [33]
Keratin, type I cytoskeletal 18 (KRT18) OTVLQFIP K1C18_HUMAN Increases Expression [34]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Increases Activity [35]
Prostate-specific antigen (KLK3) OTFGSBFJ KLK3_HUMAN Decreases Expression [36]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [32]
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Decreases Expression [37]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [38]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [39]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3) OTC1UOHP ATF3_HUMAN Decreases Expression [40]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A) OTDRV63V GA45A_HUMAN Decreases Expression [40]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Increases Activity [35]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Increases Expression [41]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [30]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [30]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [40]
Signal transducer and activator of transcription 3 (STAT3) OTAAGKYZ STAT3_HUMAN Decreases Phosphorylation [42]
Caspase-2 (CASP2) OTUDYSPP CASP2_HUMAN Increases Activity [29]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [43]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [23]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [44]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [45]
E3 ubiquitin-protein ligase Mdm2 (MDM2) OTOVXARF MDM2_HUMAN Increases Expression [7]
Focal adhesion kinase 1 (PTK2) OT3Q1JDY FAK1_HUMAN Increases Cleavage [46]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [47]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Increases Expression [27]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [46]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Activity [27]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Decreases Phosphorylation [27]
ELL-associated factor 2 (EAF2) OTSOET5L EAF2_HUMAN Decreases Expression [40]
Small integral membrane protein 14 (SMIM14) OT47IF19 SIM14_HUMAN Decreases Expression [40]
Protein FAM117A (FAM117A) OT2FBGGV F117A_HUMAN Decreases Expression [40]
Delta-like protein 4 (DLL4) OTRA4K2V DLL4_HUMAN Increases Expression [44]
Tumor necrosis factor receptor superfamily member 19 (TNFRSF19) OTTVT4MB TNR19_HUMAN Decreases Expression [40]
Tropomodulin-2 (TMOD2) OTTTUH2W TMOD2_HUMAN Decreases Expression [40]
Flavin-containing monooxygenase 3 (FMO3) OT1G2EV3 FMO3_HUMAN Affects Response To Substance [48]
Kinesin heavy chain isoform 5A (KIF5A) OT3ETTI6 KIF5A_HUMAN Decreases Response To Substance [49]
Proteinase-activated receptor 1 (F2R) OT4WVWBO PAR1_HUMAN Decreases Response To Substance [50]
ATP-binding cassette sub-family G member 1 (ABCG1) OT5BG6MK ABCG1_HUMAN Affects Response To Substance [48]
Regulator of G-protein signaling 17 (RGS17) OT5RVUDS RGS17_HUMAN Increases Response To Substance [51]
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B) OT8KME51 BUB1B_HUMAN Affects Response To Substance [52]
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Response To Substance [53]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Response To Substance [54]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Decreases Response To Substance [55]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Affects Response To Substance [48]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Increases Response To Substance [20]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Increases Response To Substance [56]
Kinesin-like protein KIFC3 (KIFC3) OTOPD4QO KIFC3_HUMAN Decreases Response To Substance [49]
Regulator of G-protein signaling 10 (RGS10) OTQ8N1QH RGS10_HUMAN Increases Response To Substance [51]
E3 ubiquitin-protein ligase CHFR (CHFR) OTRAD2TT CHFR_HUMAN Decreases Response To Substance [57]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Decreases Response To Substance [58]
Cell surface glycoprotein MUC18 (MCAM) OTT8XKGE MUC18_HUMAN Decreases Response To Substance [59]
Kinesin-like protein KIF12 (KIF12) OTTALNDD KIF12_HUMAN Decreases Response To Substance [49]
Nucleophosmin (NPM1) OTTBYYT0 NPM_HUMAN Decreases Response To Substance [60]
Flavin-containing monooxygenase 2 (FMO2) OTUJUL9S FMO2_HUMAN Affects Response To Substance [48]
NADPH--cytochrome P450 reductase (POR) OTVIDOCH NCPR_HUMAN Increases Response To Substance [20]
Kinesin-like protein KIF14 (KIF14) OTXHT4JM KIF14_HUMAN Decreases Response To Substance [61]
Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) OTXNGZCG MD2L1_HUMAN Affects Response To Substance [52]
Cellular retinoic acid-binding protein 2 (CRABP2) OTY01V9G RABP2_HUMAN Affects Response To Substance [62]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Affects Response To Substance [63]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Affects Response To Substance [48]
ATP-binding cassette sub-family C member 6 (ABCC6) OTZT0LKT MRP6_HUMAN Affects Response To Substance [48]
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⏷ Show the Full List of 83 DOT(s)
Indication(s) of GDC-0032
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 3 [4]
Solid tumour/cancer 2A00-2F9Z Phase 2/3 [5]
GDC-0032 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
PI3-kinase alpha (PIK3CA) TTEUNMR PK3CA_HUMAN Modulator [64]
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Inhibitor [4]
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References

1 ClinicalTrials.gov (NCT01862081) A Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of GDC-0032 in Combination With Docetaxel or With Paclitaxel in Patients With HER2-negative Locally Recurrent or Metastatic Breast Cancer or Non-small Cell Lung Cancer
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 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: 7794).
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.
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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
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19 Drug Interactions Flockhart Table
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22 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.
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26 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.
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29 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.
30 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.
31 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.
32 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.
33 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.
34 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.
35 The proteasome inhibitor bortezomib enhances the activity of docetaxel in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther. 2004 Jan;3(1):59-70.
36 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.
37 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.
38 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.
39 Docetaxel induced cardiotoxicity. Heart. 2001 Aug;86(2):219. doi: 10.1136/heart.86.2.219.
40 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.
41 [The mechanism of docetaxel-induced apoptosis in human lung cancer cells]. Zhonghua Zhong Liu Za Zhi. 2000 May;22(3):208-11.
42 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.
43 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.
44 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.
45 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.
46 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.
47 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.
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49 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.
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51 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.
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53 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.
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55 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.
56 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.
57 Epigenetic inactivation of the CHFR gene in cervical cancer contributes to sensitivity to taxanes. Int J Oncol. 2007 Oct;31(4):713-20.
58 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.
59 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.
60 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.
61 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.
62 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.
63 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.
64 Company report (BioOncology)