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Ref Type Journal Article
PMID (19212647)
Authors Katoh Y, Katoh M
Title FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review).
Journal International journal of molecular medicine
Vol 23
Issue 3
Date 2009 Mar
URL
Abstract Text FGFR2 gene at human chromosome 10q26 encodes FGFR2b and FGFR2c isoforms functioning as FGF receptors with distinct expression domain and ligand specificity. FGFR2 plays oncogenic and anti-oncogenic roles in a context-dependent manner. Single nucleotide polymorphisms (SNPs) within intron 2 of FGFR2 gene are associated with breast cancer through allelic FGFR2 upregulation. Missense mutations or copy number gains of FGFR2 gene occur in breast cancer and gastric cancer to activate FGFR2 signaling. Aberrant FGFR2 signaling activation induces proliferation and survival of tumor cells. The class switch from FGFR2b to FGFR2c occurs during progression of prostate cancer and bladder cancer because of spliceosome dysregulation. In addition, epidermal Fgfr2b knockout mice show increased sensitivity to chemical carcinogenesis partly due to the failure of Nfe2l2 (Nrf2)-mediated detoxification of reactive oxygen species (ROS). Loss of FGFR2b signaling induces epithelial-to-mesenchymal transition (EMT) and unruly ROS. FGFR2 signaling dysregulation due to the accumulation of epigenetic modifications and genetic alterations during chronic inflammation, smoking, increased caloric uptake, and decreased exercise leads to carcinogenesis. PD173074, SU5402, AZD2171, and Ki23057 are small-molecule FGFR inhibitors. Human antibody, peptide mimetic, RNA aptamer, siRNA, and synthetic microRNA (miRNA) are emerging technologies to be applied for cancer therapeutics targeted to FGFR2. Because novel sequence technology and peta-scale super-computer are opening up the sequence era following the genome era, personalized medicine prescribing targeted drugs based on germline and/or somatic genomic information is coming reality. Application of FGFR2 inhibitors for cancer treatment in patients with FGFR2 mutation or gene amplification is beneficial; however, that for cancer prevention in people with FGFR2 risk allele might be disadvantageous due to the impediment of a cytoprotective mechanism against oxidative stress.

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Molecular Profile Treatment Approach
FGFR2 C342Y FGFR2 Inhibitor
FGFR2 K660N FGFR2 Inhibitor
FGFR2 R678G FGFR2 Inhibitor
FGFR2 H416R FGFR2 Inhibitor
FGFR2 - CCDC6 FGFR2 Inhibitor
FGFR2 I547V FGFR2 Inhibitor
FGFR2 N550S FGFR2 Inhibitor
FGFR2 E566G FGFR2 Inhibitor
FGFR2 E566A FGFR2 Inhibitor
FGFR2 K525E FGFR2 Inhibitor
FGFR2 V565I FGFR2 Inhibitor
FGFR2 V564L FGFR2 Inhibitor
FGFR2 S354C FGFR2 Inhibitor
FGFR2 S372C FGFR2 Inhibitor
FGFR2 E565A FGFR2 Inhibitor
FGFR2 - FAM76A FGFR2 Inhibitor
FGFR2 C383R FGFR2 Inhibitor
FGFR2 act mut FGFR2 Inhibitor
FGFR2 N549T FGFR2 Inhibitor
FGFR2 E163K FGFR2 Inhibitor
FGFR2 P253R FGFR2 Inhibitor
FGFR2 K659M FGFR2 Inhibitor
FGFR2 N550T FGFR2 Inhibitor
FGFR2 V564I FGFR2 Inhibitor
FGFR2 E718K FGFR2 Inhibitor
FGFR2 L618M FGFR2 Inhibitor
FGFR2 G364E FGFR2 Inhibitor
FGFR2 N82K FGFR2 Inhibitor
FGFR2 - PPHLN1 FGFR2 Inhibitor
FGFR2 N549H FGFR2 Inhibitor
FGFR2 I548V FGFR2 Inhibitor
FGFR2 D101Y FGFR2 Inhibitor
FGFR2 N550K FGFR2 Inhibitor
FGFR2 K641N FGFR2 Inhibitor
FGFR2 S252W FGFR2 Inhibitor
FGFR2 V564F FGFR2 Inhibitor
FGFR2 - AHCYL1 FGFR2 Inhibitor
FGFR2 W290_I291delinsC FGFR2 Inhibitor
FGFR2 K659N FGFR2 Inhibitor
FGFR2 N549S FGFR2 Inhibitor
FGFR2 K659E FGFR2 Inhibitor
FGFR2 E160K FGFR2 Inhibitor
FGFR2 R203C FGFR2 Inhibitor
FGFR2 L617V FGFR2 Inhibitor
FGFR2 amp FGFR2 Inhibitor
FGFR2 M537I FGFR2 Inhibitor
FGFR2 M536I FGFR2 Inhibitor
FGFR2 K526E FGFR2 Inhibitor
FGFR2 L560F FGFR2 Inhibitor
FGFR2 V392A FGFR2 Inhibitor
FGFR2 C382R FGFR2 Inhibitor
FGFR2 R399Q FGFR2 Inhibitor
FGFR2 C342R FGFR2 Inhibitor
FGFR2 E565G FGFR2 Inhibitor
FGFR2 - BICC1 FGFR2 Inhibitor
FGFR2 P253L FGFR2 Inhibitor
FGFR2 K660E FGFR2 Inhibitor
FGFR2 M538I FGFR2 Inhibitor
FGFR2 C62Y FGFR2 Inhibitor
FGFR2 D650A FGFR2 Inhibitor
FGFR2 N549D FGFR2 Inhibitor
FGFR2 - DNM3 FGFR2 Inhibitor
FGFR2 W290C FGFR2 Inhibitor
FGFR2 G663E FGFR2 Inhibitor
FGFR2 Y376C FGFR2 Inhibitor
FGFR2 T341P FGFR2 Inhibitor
FGFR2 Y328N FGFR2 Inhibitor
FGFR2 N549K FGFR2 Inhibitor
FGFR2 D650I FGFR2 Inhibitor
FGFR2 Y375C FGFR2 Inhibitor
FGFR2 F276C FGFR2 Inhibitor
FGFR2 K310R FGFR2 Inhibitor
FGFR2 over exp FGFR2 Inhibitor
FGFR2 K642R FGFR2 Inhibitor
FGFR2 - TACC3 FGFR2 Inhibitor
FGFR2 K641R FGFR2 Inhibitor
FGFR2 D650L FGFR2 Inhibitor
FGFR2 A67V FGFR2 Inhibitor
FGFR2 A264T FGFR2 Inhibitor
FGFR2 I422V FGFR2 Inhibitor
FGFR2 N550H FGFR2 Inhibitor
FGFR2 S267_D273dup FGFR2 Inhibitor
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References