Molecule Information

General Information of the Molecule (ID: Mol01183)
Name
Fibroblast growth factor receptor (FGFR) ,Homo sapiens
Molecule Type
Protein
Gene Name
FGFR
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
4 drug(s) in total
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Cisplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Bladder cancer [ICD-11: 2C94.0] [1]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug Cisplatin
 Drug Info 
Molecule Alteration Function
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation FGFR/PI3K/AKT signaling pathway Regulation N.A.
FGFR/RAS/MAPK signaling pathway Regulation N.A.
In Vitro Model T24 cells Bladder Homo sapiens (Human) CVCL_0554
J82 cells Bladder Homo sapiens (Human) CVCL_0359
In Vivo Model BALB/c female nude mice model Mus musculus
Experiment for
Molecule Alteration		 MS analysis; Western blot assay; Immunohistochemistry
Experiment for
Drug Resistance		 IC50 assay; Cell proliferation assay; Migration ability assay; Invasion ability assay; Apoptosis assay
Mechanism Description Cisplatin-resistant cells showed elevated fatty acid metabolism, upregulating fatty acid synthase (FASN) downstream of tyrosine kinase. Using the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor erdafitinib, we inhibited malonyl-CoA production, which is crucial for fatty acid synthesis, and thereby suppressed upregulated HIF1alpha expression. Combination treatment with NCT503 and erdafitinib synergistically suppressed tumor cell proliferation and induced apoptosis in?vitro and in?vivo. Understanding these mechanisms could enable innovative BC therapeutic strategies to be developed.
LY2835219
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer [ICD-11: 2C60.3] [2]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Resistant Drug LY2835219
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation FGFR signaling pathway Activation hsa01521
PI3K/AKT signaling pathway Inhibition hsa05235
RAS/MEK/ERK signaling pathway Activation hsa04010
Mechanism Description The FGFR pathway is frequently activated in several types of cancer, including breast cancer. Of the five FGFRs, FGFR 1-4 have been reported to play an important role in cancer progression. Furthermore, FGFR1 and FGFR2 also appear to be associated with resistance to CDK4/6 inhibitors, as well as with endocrine resistance. Mechanistic investigation showed that FGFR1 amplification activated the PI3K/AKT and RAS/MEK/ERK signaling pathways in endocrine-resistant breast cancer cells.
Palbociclib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer [ICD-11: 2C60.3] [2]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Resistant Drug Palbociclib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation FGFR signaling pathway Activation hsa01521
PI3K/AKT signaling pathway Inhibition hsa05235
RAS/MEK/ERK signaling pathway Activation hsa04010
Mechanism Description The FGFR pathway is frequently activated in several types of cancer, including breast cancer. Of the five FGFRs, FGFR 1-4 have been reported to play an important role in cancer progression. Furthermore, FGFR1 and FGFR2 also appear to be associated with resistance to CDK4/6 inhibitors, as well as with endocrine resistance. Mechanistic investigation showed that FGFR1 amplification activated the PI3K/AKT and RAS/MEK/ERK signaling pathways in endocrine-resistant breast cancer cells.
Ribociclib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Breast cancer [ICD-11: 2C60.3] [2]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Resistant Drug Ribociclib
 Drug Info 
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation FGFR signaling pathway Activation hsa01521
PI3K/AKT signaling pathway Inhibition hsa05235
RAS/MEK/ERK signaling pathway Activation hsa04010
Mechanism Description The FGFR pathway is frequently activated in several types of cancer, including breast cancer. Of the five FGFRs, FGFR 1-4 have been reported to play an important role in cancer progression. Furthermore, FGFR1 and FGFR2 also appear to be associated with resistance to CDK4/6 inhibitors, as well as with endocrine resistance. Mechanistic investigation showed that FGFR1 amplification activated the PI3K/AKT and RAS/MEK/ERK signaling pathways in endocrine-resistant breast cancer cells.
Investigative Drug(s)
1 drug(s) in total
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FGFR inhibitors
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Glioblastoma [ICD-11: 2A00.02] [3]
Resistant Disease Glioblastoma [ICD-11: 2A00.02]
 Disease Info 
Resistant Drug FGFR inhibitors
 Drug Info 
Molecule Alteration Chromosomal translocations
FGFR-TACC gene fusions
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation ERK/MAPKsignaling pathway Activation hsa04210
PI3K/AKT signaling pathway Activation hsa04151
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.
Disease Class: Bladder cancer [ICD-11: 2C94.0] [4]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug FGFR inhibitors
 Drug Info 
Molecule Alteration Mutation
.
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation ERK/MAPKsignaling pathway Activation hsa04210
PI3K/AKT signaling pathway Activation hsa04151
STAT3 signaling pathway Activation hsa04550
In Vitro Model 639V cells Bladder Homo sapiens (Human) CVCL_1048
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 Targeting metabolic reprogramming to overcome drug resistance in advanced bladder cancer: insights from gemcitabine- and cisplatin-resistant models. Mol Oncol. 2024 Sep;18(9):2196-2211.
Ref 2 Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review .Int J Cancer. 2019 Sep 1;145(5):1179-1188. doi: 10.1002/ijc.32020. Epub 2019 Jan 7. 10.1002/ijc.32020
Ref 3 FGFR-TACC gene fusions in human glioma. Neuro Oncol. 2017 Apr 1;19(4):475-483. doi: 10.1093/neuonc/now240.
Ref 4 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.

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