Drug Information

Drug (ID: DG01728) and It's Reported Resistant Information
Name
EGFR TKIs
Synonyms
EGFR TKIs
    Click to Show/Hide
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Brain cancer [ICD-11: 2A00]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Lung cancer [ICD-11: 2C25]
[2]
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Brain cancer [ICD-11: 2A00]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [3]
Resistant Disease Brain glioma [ICD-11: 2A00.0]
 Disease Info 
Molecule Alteration IF-deletion
p.V30_V336 (c.88_1008)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Brain N.A.
Mechanism Description The if-deletion p.V30_V336 (c.88_1008) in gene EGFR cause the resistance of EGFR TKIs by aberration of the drug's therapeutic target.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease Brain glioma [ICD-11: 2A00.0]
 Disease Info 
Molecule Alteration Copy number gain
.
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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420
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440
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470
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480
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490
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500
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510
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530
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540
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580
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590
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600
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660
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670
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680
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690
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
HCC827 cells Lung Homo sapiens (Human) CVCL_2063
HCC4006 cells Lung Homo sapiens (Human) CVCL_1269
PC9 cells Lung Homo sapiens (Human) CVCL_B260
HCC4011 cells Lung Homo sapiens (Human) CVCL_S700
11-18 cells Lung Homo sapiens (Human) CVCL_6659
In Vivo Model Nude mouse (nu/nu; Harlan Laboratories) xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Cell Titer blue reagent assay
Mechanism Description The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the resistance of EGFR TKIs by aberration of the drug's therapeutic target
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G469A (c.1406G>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
HCC827 cells Lung Homo sapiens (Human) CVCL_2063
HCC4006 cells Lung Homo sapiens (Human) CVCL_1269
PC9 cells Lung Homo sapiens (Human) CVCL_B260
HCC4011 cells Lung Homo sapiens (Human) CVCL_S700
11-18 cells Lung Homo sapiens (Human) CVCL_6659
In Vivo Model Nude mouse (nu/nu; Harlan Laboratories) xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting assay
Experiment for
Drug Resistance		 Cell Titer blue reagent assay
Mechanism Description The missense mutation p.G469A (c.1406G>C) in gene BRAF cause the resistance of EGFR TKIs by aberration of the drug's therapeutic target
References
Ref 1 Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01Clin Cancer Res. 2005 Nov 1;11(21):7841-50. doi: 10.1158/1078-0432.CCR-05-0421.
Ref 2 Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2127-33. doi: 10.1073/pnas.1203530109. Epub 2012 Jul 6.
Ref 3 Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034J Clin Oncol. 2009 Mar 10;27(8):1268-74. doi: 10.1200/JCO.2008.17.5984. Epub 2009 Feb 9.

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