Drug Details

General Information of the Drug (ID: DR6300)
Name
Trastuzumab
Synonyms
Herceptin; Herceptin (TN); Trastuzumab (INN); Trastuzumab (genetical recombination); Trastuzumab (genetical recombination) (JAN); Trastuzumab (ERBB2 mAb inhibitor)
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Molecular Type
Antibody
Disease Breast cancer [ICD-11: 2C60] Approved [1]
ADMET Property
Clearance
The clearance of drug is 0.173-0.337 L/day
Half-life
The concentration or amount of drug in body reduced by one-half in 28 days
Metabolism
The drug is metabolized via the intracellularly into smaller peptides and amino acids
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TTD Drug ID
D04WFL
DrugBank ID
DB00072
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Celastrol      Celastrus strigillosus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression c-RAF  Molecule Info 
Pathway MAP
Down-regulation Expression HER2  Molecule Info 
Pathway MAP
Down-regulation Expression HSPA4  Molecule Info 
Pathway MAP
                    In-vitro Model SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
BT-20 CVCL_0178 Invasive breast carcinoma Homo sapiens
MCF-10A CVCL_0598 Healthy Homo sapiens
                    In-vivo Model Four to six week old female NOD-SCID mice received sub-cutaneous 17Beta-estradiol pellet (0.72 mg/day), 2 weeks prior to injection of 5 * 106 BT-474 cells resuspended in 4% Matrigel.
                    Experimental
                    Result(s)		 Celastrol strongly synergized with ErbB2-targeted therapeutics Trastuzumab, producing higher cytotoxicity with substantially lower doses of Celastrol.
          Flavopiridol      Dysoxylum binectariferum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-453 CVCL_0418 Breast adenocarcinoma Homo sapiens
BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Synergy between flavopiridol and trastuzumab can result from enhanced apoptosis, and that combination effects on EGFR expression are involved in the interaction.
          Genistein      Glycine max     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Genistein significantly enhanced the antitumoral effect of trastuzumab on BT-474 breast cancer cells in vitro.
          Osthole      Angelica pubescens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-N87 CVCL_1603 Gastric tubular adenocarcinoma Homo sapiens
                    In-vivo Model N87 cells (1*107/per mouse) were inoculated subcutaneously into the right flank of female BALB/c nude mice.
                    Experimental
                    Result(s)		 Osthole synergizes with trastuzumab in HER2-overexpressed N87 gastric cancer by inducing apoptosis and inhibition of AKT-MAPK pathway.
          Paclitaxel      Taxus brevifolia     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model BT-474 CVCL_0179 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Trastuzumab and paclitaxel combination showed synergistic therapy for HER2+ breast cancer.
          Resveratrol      Gnetum parvifolium     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Down-regulation Expression HER2  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
T-47D CVCL_0553 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Herceptin / resveratrol combinations improved the cytotoxic profile of herceptin in both T47D and MCF-7 breast cancer cell lines.
Target and Pathway
Target(s) Tyrosine kinase receptor Erbb2 (HER2)  Molecule Info  [8]
KEGG Pathway ErbB signaling pathway Click to Show/Hide
2 Calcium signaling pathway
3 HIF-1 signaling pathway
4 Focal adhesion
5 Adherens junction
6 Pathways in cancer
7 Proteoglycans in cancer
8 MicroRNAs in cancer
9 Pancreatic cancer
10 Endometrial cancer
11 Prostate cancer
12 Bladder cancer
13 Non-small cell lung cancer
14 Central carbon metabolism in cancer
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
Panther Pathway Cadherin signaling pathway Click to Show/Hide
2 EGF receptor signaling pathway
Pathwhiz Pathway Phosphatidylinositol Phosphate Metabolism Click to Show/Hide
Pathway Interaction Database ErbB4 signaling events Click to Show/Hide
2 ErbB2/ErbB3 signaling events
3 ErbB receptor signaling network
4 a6b1 and a6b4 Integrin signaling
5 Validated targets of C-MYC transcriptional repression
Reactome SHC1 events in ERBB2 signaling Click to Show/Hide
2 PLCG1 events in ERBB2 signaling
3 PIP3 activates AKT signaling
4 GRB2 events in ERBB2 signaling
5 PI3K events in ERBB2 signaling
6 Constitutive Signaling by Aberrant PI3K in Cancer
7 Sema4D induced cell migration and growth-cone collapse
8 RAF/MAP kinase cascade
WikiPathways DNA Damage Response (only ATM dependent) Click to Show/Hide
2 ErbB Signaling Pathway
3 EGF/EGFR Signaling Pathway
4 Focal Adhesion
5 Extracellular vesicle-mediated signaling in recipient cells
6 Bladder Cancer
7 Signaling by ERBB2
8 Integrated Pancreatic Cancer Pathway
9 Signaling Pathways in Glioblastoma
10 Leptin signaling pathway
11 miR-targeted genes in muscle cell - TarBase
12 Semaphorin interactions
References
Reference 1 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: 5082).
Reference 2 Anticancer activity of Celastrol in combination with ErbB2-targeted therapeutics for treatment of ErbB2-overexpressing breast cancers. Cancer Biol Ther. 2011 Jan 15;11(2):263-76.
Reference 3 Epidermal growth factor receptor expression is a candidate target of the synergistic combination of trastuzumab and flavopiridol in breast cancer. Cancer Res. 2003 Jul 1;63(13):3626-31.
Reference 4 Additive effects of trastuzumab and genistein on human breast cancer cells. Anticancer Drugs. 2011 Mar;22(3):253-61.
Reference 5 Osthole Synergizes With HER2 Inhibitor, Trastuzumab in HER2-Overexpressed N87 Gastric Cancer by Inducing Apoptosis and Inhibition of AKT-MAPK Pathway. Front Pharmacol. 2018 Nov 27;9:1392.
Reference 6 Experimentally-driven mathematical modeling to improve combination targeted and cytotoxic therapy for HER2+ breast cancer. Sci Rep. 2019 Sep 6;9(1):12830.
Reference 7 The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines. Sci Rep. 2015 Jul 9;5:12054.
Reference 8 Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res. 2004 Jun;14(3):207-10.
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