Drug Information

Drug (ID: DG01728) and It's Reported Resistant Information

• Name: EGFR TKIs
• Synonyms: EGFR TKIs
• 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]
• Target: .; NOUNIPROTAC; [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

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Molecule Alteration: IF-deletion; p.V30_V336 (c.88_1008)
• Resistant Disease: Brain glioma [ICD-11: 2A00.0]
• 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]

• Molecule Alteration: Copy number gain; .
• Resistant Disease: Brain glioma [ICD-11: 2A00.0]
• Experimental Note: Identified from the Human Clinical Data

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: HCC4006 cells; Lung; Homo sapiens (Human); CVCL_1269
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: HCC4011 cells; Lung; Homo sapiens (Human); CVCL_S700
• In Vitro Model: 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]

• Molecule Alteration: Missense mutation; p.G469A (c.1406G>C)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: HCC4006 cells; Lung; Homo sapiens (Human); CVCL_1269
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: HCC4011 cells; Lung; Homo sapiens (Human); CVCL_S700
• In Vitro Model: 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.