Drug Information

Drug (ID: DG01764) and It's Reported Resistant Information

• Name: Futuximab
• Synonyms: Futuximab
• Target: .; NOUNIPROTAC; [1]

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.R451C (c.1351C>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.K467T (c.1400A>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.R451C (c.1351C>T)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.G465R (c.1393G>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.K467T (c.1400A>C)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.S492R (c.1476C>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: EGFR signaling pathway; Regulation; hsa01521
• In Vitro Model: LIM1215 cells; Colon; Homo sapiens (Human); CVCL_2574
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• In Vitro Model: EGFR cells; N.A.; .; N.A.
• In Vivo Model: Male BALB/c nude mouse; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Promega assay; FACS assay; Crystal violet staining assay
• Mechanism Description: Contrary to cetuximab and panitumumab, Sym004 effectively binds to and prevents activation of all the EGFR mutants. Sym004 effectively inhibits proliferation and EGFR downstream signaling in cetuximab-resistant derivatives harboring the S492R and G465R EGFR mutations. Sym004 causes profound and sustained regression in S492R-mutant EGFR and delays tumor growth in G465R-mutant EGFR in vivo.

Key Molecule: Epidermal growth factor receptor (EGFR) [2]

• Molecule Alteration: Missense mutation; p.S492R (c.1476C>G)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: DLD1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: LS1034 cells; Colon; Homo sapiens (Human); CVCL_1382
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vitro Model: GEO cells; Colon; Homo sapiens (Human); CVCL_0271
• In Vitro Model: HCT15 cells; Colon; Homo sapiens (Human); CVCL_0292
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: LS174T cells; Colon; Homo sapiens (Human); CVCL_1384
• In Vitro Model: SW948 cells; Colon; Homo sapiens (Human); CVCL_0632
• In Vitro Model: SW403 cells; Colon; Homo sapiens (Human); CVCL_0545
• In Vitro Model: SW837 cells; Colon; Homo sapiens (Human); CVCL_1729
• In Vitro Model: T84 cells; Colon; Homo sapiens (Human); CVCL_0555
• In Vitro Model: SW1463 cells; Rectum; Homo sapiens (Human); CVCL_1718
• In Vitro Model: H716 cells; Ascites; Homo sapiens (Human); CVCL_1581
• In Vitro Model: H508 cells; Abdominal wall; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SNUC2A cells; Cecum; Homo sapiens (Human); CVCL_1709
• In Vitro Model: COLO678 cells; Colon; Homo sapiens (Human); CVCL_1129
• In Vitro Model: GP5D cells; Colon; Homo sapiens (Human); CVCL_1235
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: WST-1 assay

References

• Ref 1: The First-in-class Anti-EGFR Antibody Mixture Sym004 Overcomes Cetuximab Resistance Mediated by EGFR Extracellular Domain Mutations in Colorectal CancerClin Cancer Res. 2016 Jul 1;22(13):3260-7. doi: 10.1158/1078-0432.CCR-15-2400. Epub 2016 Feb 17.
• Ref 2: Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal CancerCancer Discov. 2015 Jun;5(6):598-609. doi: 10.1158/2159-8290.CD-14-1432. Epub 2015 May 11.