Molecule Information

General Information of the Molecule (ID: Mol01183)

• Name: Fibroblast growth factor receptor (FGFR) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: FGFR

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) 3 drug(s) in total

LY2835219

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: LY2835219
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FGFR signaling pathway; Activation; hsa01521
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa05235
• Cell Pathway Regulation: 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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Palbociclib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FGFR signaling pathway; Activation; hsa01521
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa05235
• Cell Pathway Regulation: 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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Ribociclib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FGFR signaling pathway; Activation; hsa01521
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa05235
• Cell Pathway Regulation: 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

FGFR inhibitors

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Glioblastoma [2]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: FGFR inhibitors
• Molecule Alteration: Chromosomal translocations; FGFR-TACC gene fusions
• 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.

Disease Class: Bladder cancer [3]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Resistant Drug: FGFR inhibitors
• Molecule Alteration: Mutation; .
• 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: 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 2: FGFR-TACC gene fusions in human glioma. Neuro Oncol. 2017 Apr 1;19(4):475-483. doi: 10.1093/neuonc/now240.
• Ref 3: 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.