Drug Details

General Information of the Drug (ID: DR5221)
Name
Cetuximab
Synonyms
Erbitux; Cetuximab (genetical recombination); Erbitux (TN); Cetuximab (USAN/INN); Cetuximab (genetical recombination) (JAN); novel EGFR mAb inhibitors
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Molecular Type
Antibody
Disease Colorectal cancer [ICD-11: 2B91] Approved [1]
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 3 h
Clearance
The sytemic clearance of drug is 0.103 L/h
Half-life
The concentration or amount of drug in body reduced by one-half in 112 hours
Metabolism
The drug is metabolized via the reticuloendothelial system and protein catabolism by a target\mediated disposition pathway
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
GDSC
Cetuximab
TTD Drug ID
D0N5OV
DrugBank ID
DB00002
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Apigenin      Psilotum nudum     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     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 CCND1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation STAT3  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2/M phase
                    In-vitro Model HONE-1 CVCL_8706 Nasopharyngeal carcinoma Homo sapiens
CNE-2 CVCL_6889 Human nasopharyngeal carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling.
          Cidofovir      Homo sapiens     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		 Up-regulation Phosphorylation H2AFX  Molecule Info 
Pathway MAP
                    In-vitro Model HeLa CVCL_0030 Endocervical adenocarcinoma Homo sapiens
ME-180 CVCL_1401 Cervical squamous cell carcinoma Homo sapiens
C-33 A CVCL_1094 Cervical squamous cell carcinoma Homo sapiens
                    In-vivo Model For a xenograft model, cells (2*106 Me180, HeLa, or C33A) were injected subcutaneously into female nude mice aged 10-12weeks (Elevage Janvier).
                    Experimental
                    Result(s)		 Cidofovir and Cetuximab have synergistic antitumor effect in HPV-positive tumors.
          Curcumin      Hellenia speciosa     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
                    Molecule(s)
                    Regulation		 Up-regulation Activity CASP3  Molecule Info 
Pathway MAP
Up-regulation Activity CASP9  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
                    In-vitro Model CAL-27 CVCL_1107 Tongue squamous cell carcinoma Homo sapiens
CAR CVCL_4140 Human oral cancer Carassius auratus
                    Experimental
                    Result(s)		 Co-treatment with cetuximab and curcumin exerts synergistic oral anticancer effects on CAR cells through the suppression of the EGFR signaling by regulation of the MAPK pathway.
          Elemene      Pogostemon cablin     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 Expression CDH1  Molecule Info 
Pathway MAP
Up-regulation Expression CDH1  Molecule Info 
Pathway MAP
Down-regulation Expression CDH2  Molecule Info 
Pathway MAP
Down-regulation Expression GLS2  Molecule Info 
Pathway MAP
Down-regulation Expression GPX4  Molecule Info 
Pathway MAP
Down-regulation Expression HMOX1  Molecule Info 
Pathway MAP
Up-regulation Expression HMOX1  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression SLC40A1  Molecule Info 
Pathway MAP
Down-regulation Expression SLC7A11  Molecule Info 
Pathway MAP
Down-regulation Expression SNAI1  Molecule Info 
Pathway MAP
Down-regulation Expression SNAI2  Molecule Info 
Pathway MAP
Down-regulation Expression TF  Molecule Info 
Pathway MAP
Up-regulation Expression TF  Molecule Info 
Pathway MAP
Down-regulation Expression VIM  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    In-vivo Model A volume of 100 ul HCT116-luc cells suspension (2.5*106 cells/ml) was injected subcutaneously into right dorsal flank of mice (5-week-old female BALB/c nude mice).
                    Experimental
                    Result(s)		 Combinative treatment of Beta-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation.
          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 [6]
                    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 Phosphorylation EGFR  Molecule Info 
Pathway MAP
                    In-vitro Model HSC-3 CVCL_1288 Tongue squamous cell carcinoma Homo sapiens
KB CVCL_0372 Oral squamous cell carcinoma Homo sapiens
                    In-vivo Model HSC3 cells (1*107) were inoculated subcutaneously into the right flank of total eighty 6-8-week-old female BALB/c nude mice.
                    Experimental
                    Result(s)		 Combined cetuximab and genistein treatment shows additive anti-cancer effect on oral squamous cell carcinoma.
          Oridonin      Isodon rubescens     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		 Up-regulation Expression BECN1  Molecule Info 
Pathway MAP
Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Expression mTOR  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Expression PRKAA2  Molecule Info 
Pathway MAP
Up-regulation Phosphorylation PRKAA2  Molecule Info 
Pathway MAP
                    In-vitro Model HEp-2 CVCL_1906 Laryngeal carcinoma Homo sapiens
Tu 212 CVCL_4915 Head and neck squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Autophagy might be strongly associated with the antitumor efficacy of ORI/Cet, which may be beneficial to the clinical application of ORI/Cet in LSCC treatment ORI/Cet in LSCC treatment.
          Resveratrol      Gnetum parvifolium     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression PLAUR  Molecule Info 
Pathway MAP
                    In-vitro Model SAS CVCL_1675 Tongue squamous cell carcinoma Homo sapiens
Sa3 CVCL_8063 Gingival squamous cell carcinoma Homo sapiens
HSC-3 CVCL_1288 Tongue squamous cell carcinoma Homo sapiens
                    In-vivo Model SAS-R or Sa3-R cells (1*106) were injected subcutaneously into the backs of the female athymic nude mice.
                    Experimental
                    Result(s)		 Resveratrol targets Urokinase-type plasminogen activator receptor expression to overcome cetuximab-resistance in oral squamous cell carcinoma.
          Triptolide      Tripterygium hypoglaucum     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 [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CASP3  Molecule Info 
Pathway MAP
Down-regulation Expression POLR2A  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
UM-SCC-6 CVCL_7773 Tongue squamous cell carcinoma Homo sapiens
NCI-H520 CVCL_1566 Lung squamous cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Cetuximab-Triptolide conjugate suppresses the growth of EGFR-overexpressing lung cancers through targeting RNA polymerase II.
Target and Pathway
Target(s) Epidermal growth factor receptor (EGFR)  Molecule Info  [10]
KEGG Pathway MAPK signaling pathway Click to Show/Hide
2 ErbB signaling pathway
3 Ras signaling pathway
4 Rap1 signaling pathway
5 Calcium signaling pathway
6 Cytokine-cytokine receptor interaction
7 HIF-1 signaling pathway
8 FoxO signaling pathway
9 Endocytosis
10 PI3K-Akt signaling pathway
11 Dorso-ventral axis formation
12 Focal adhesion
13 Adherens junction
14 Gap junction
15 Regulation of actin cytoskeleton
16 GnRH signaling pathway
17 Estrogen signaling pathway
18 Oxytocin signaling pathway
19 Epithelial cell signaling in Helicobacter pylori infection
20 Hepatitis C
21 Pathways in cancer
22 Proteoglycans in cancer
23 MicroRNAs in cancer
24 Pancreatic cancer
25 Endometrial cancer
26 Glioma
27 Prostate cancer
28 Melanoma
29 Bladder cancer
30 Non-small cell lung cancer
31 Central carbon metabolism in cancer
32 Choline metabolism in cancer
NetPath Pathway IL4 Signaling Pathway Click to Show/Hide
2 EGFR1 Signaling Pathway
Panther Pathway Cadherin signaling pathway Click to Show/Hide
2 EGF receptor signaling pathway
Pathway Interaction Database LPA receptor mediated events Click to Show/Hide
2 Signaling events mediated by PTP1B
3 Arf6 signaling events
4 Signaling events mediated by TCPTP
5 Thromboxane A2 receptor signaling
6 SHP2 signaling
7 Regulation of Telomerase
8 EGF receptor (ErbB1) signaling pathway
9 EGFR-dependent Endothelin signaling events
10 Posttranslational regulation of adherens junction stability and dissassembly
11 Direct p53 effectors
12 ErbB1 downstream signaling
13 Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
14 E-cadherin signaling in keratinocytes
15 ErbB receptor signaling network
16 Internalization of ErbB1
17 Stabilization and expansion of the E-cadherin adherens junction
18 a6b1 and a6b4 Integrin signaling
19 Syndecan-3-mediated signaling events
Reactome Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants Click to Show/Hide
2 SHC1 events in ERBB2 signaling
3 PLCG1 events in ERBB2 signaling
4 PIP3 activates AKT signaling
5 GRB2 events in EGFR signaling
6 GAB1 signalosome
7 SHC1 events in EGFR signaling
8 EGFR downregulation
9 GRB2 events in ERBB2 signaling
10 PI3K events in ERBB2 signaling
11 EGFR Transactivation by Gastrin
12 Constitutive Signaling by Aberrant PI3K in Cancer
13 Constitutive Signaling by EGFRvIII
14 RAF/MAP kinase cascade
WikiPathways ErbB Signaling Pathway Click to Show/Hide
2 Regulation of Actin Cytoskeleton
3 EGF/EGFR Signaling Pathway
4 MAPK Signaling Pathway
5 Focal Adhesion
6 Aryl Hydrocarbon Receptor Pathway
7 Extracellular vesicle-mediated signaling in recipient cells
8 TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
9 Hair Follicle Development: Cytodifferentiation (Part 3 of 3)
10 Bladder Cancer
11 Hair Follicle Development: Induction (Part 1 of 3)
12 Signaling by ERBB4
13 Signaling by ERBB2
14 Gastrin-CREB signalling pathway via PKC and MAPK
15 PIP3 activates AKT signaling
16 Nanoparticle-mediated activation of receptor signaling
17 Aryl Hydrocarbon Receptor
18 Spinal Cord Injury
19 Integrated Pancreatic Cancer Pathway
20 Gastric cancer network 2
21 AGE/RAGE pathway
22 Signaling Pathways in Glioblastoma
23 Arylhydrocarbon receptor (AhR) signaling pathway
24 miR-targeted genes in muscle cell - TarBase
25 miR-targeted genes in lymphocytes - TarBase
26 miR-targeted genes in epithelium - TarBase
27 Integrated Breast Cancer Pathway
28 Signaling by EGFR
29 L1CAM 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: 6882).
Reference 2 Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling. Biomed Pharmacother. 2018 Jun;102:681-688.
Reference 3 The combination of the antiviral agent cidofovir and anti-EGFR antibody cetuximab exerts an antiproliferative effect on HPV-positive cervical cancer cell lines' in-vitro and in-vivo xenografts. Anticancer Drugs. 2013 Jul;24(6):599-608.
Reference 4 Synergistic inhibitory effects of cetuximab and curcumin on human cisplatin-resistant oral cancer CAR cells through intrinsic apoptotic process. Oncol Lett. 2018 Nov;16(5):6323-6330.
Reference 5 Combinative treatment of beta-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation. Theranostics. 2020 Apr 6;10(11):5107-5119.
Reference 6 Combined cetuximab and genistein treatment shows additive anti-cancer effect on oral squamous cell carcinoma. Cancer Lett. 2010 Jun 1;292(1):54-63.
Reference 7 Molecular mechanisms of apoptosis and autophagy elicited by combined treatment with oridonin and cetuximab in laryngeal squamous cell carcinoma. Apoptosis. 2019 Feb;24(1-2):33-45.
Reference 8 Resveratrol Targets Urokinase-Type Plasminogen Activator Receptor Expression to Overcome Cetuximab-Resistance in Oral Squamous Cell Carcinoma. Sci Rep. 2019 Aug 21;9(1):12179.
Reference 9 Cetuximab-Triptolide Conjugate Suppresses the Growth of EGFR-Overexpressing Lung Cancers through Targeting RNA Polymerase II. Mol Ther Oncolytics. 2020 Jul 6;18:304-316.
Reference 10 Molecular inhibition of angiogenesis and metastatic potential in human squamous cell carcinomas after epidermal growth factor receptor blockade. Mol Cancer Ther. 2002 May;1(7):507-14.
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