Drug Information

Drug (ID: DG00485) and It's Reported Resistant Information

• Name: FGFR inhibitors
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Bladder cancer [ICD-11: 2C94]; [1]
  Brain cancer [ICD-11: 2A00]; [2]
  COVID-19 [ICD-11: 1D92]; [3]

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: Fibroblast growth factor receptor (FGFR) [2]

• Molecule Alteration: Chromosomal translocations; FGFR-TACC gene fusions
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK/MAPKsignaling pathway; Activation; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• Experiment for Molecule Alteration: Sanger sequencing assay
• Experiment for Drug Resistance: Screening assay
• Mechanism Description: In particular, epidermal growth factor receptor (EGFR) activation has been identified as a mechanism of resistance in bladder cancer cells with FGFR3 mutations after treatment with FGFR inhibitors.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hepatocyte growth factor receptor (MET) [2]

• Molecule Alteration: Mutation; .
• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK/MAPKsignaling pathway; Activation; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• Experiment for Molecule Alteration: Sanger sequencing assay
• Experiment for Drug Resistance: Screening assay
• Mechanism Description: In particular, epidermal growth factor receptor (EGFR) activation has been identified as a mechanism of resistance in bladder cancer cells with FGFR3 mutations after treatment with FGFR inhibitors.

Bladder cancer [ICD-11: 2C94]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Fibroblast growth factor receptor (FGFR) [1]

• Molecule Alteration: Mutation; .
• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK/MAPKsignaling pathway; Activation; hsa04210
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• In Vitro Model: 639V cells; Bladder; Homo sapiens (Human); CVCL_1048
• In Vitro Model: MGHU3 cells; Bladder; Homo sapiens (Human); CVCL_9827
• Experiment for Molecule Alteration: Sanger sequencing assay
• Experiment for Drug Resistance: Screening assay
• Mechanism Description: In particular, epidermal growth factor receptor (EGFR) activation has been identified as a mechanism of resistance in bladder cancer cells with FGFR3 mutations after treatment with FGFR inhibitors.

References

• Ref 1: Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3-mutant cancer. Cancer Discov. 2013 Sep;3(9):1058-71. doi: 10.1158/2159-8290.CD-12-0569. Epub 2013 Jun 6.
• Ref 2: FGFR-TACC gene fusions in human glioma. Neuro Oncol. 2017 Apr 1;19(4):475-483. doi: 10.1093/neuonc/now240.
• Ref 3: Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 Nature. 2021 May;593(7857):130-135. doi: 10.1038/s41586-021-03398-2. Epub 2021 Mar 8.