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Ref Type Journal Article
PMID (24265351)
Authors Dienstmann R, Rodon J, Prat A, Perez-Garcia J, Adamo B, Felip E, Cortes J, Iafrate AJ, Nuciforo P, Tabernero J
Title Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors.
Journal Annals of oncology : official journal of the European Society for Medical
Vol 25
Issue 3
Date 2014 Mar
URL
Abstract Text The fibroblast growth factor receptor (FGFR) cascade plays crucial roles in tumor cell proliferation, angiogenesis, migration and survival. Accumulating evidence suggests that in some tumor types, FGFRs are bona fide oncogenes to which cancer cells are addicted. Because FGFR inhibition can reduce proliferation and induce cell death in a variety of in vitro and in vivo tumor models harboring FGFR aberrations, a growing number of research groups have selected FGFRs as targets for anticancer drug development. Multikinase FGFR/vascular endothelial growth factor receptor (VEGFR) inhibitors have shown promising activity in breast cancer patients with FGFR1 and/or FGF3 amplification. Early clinical trials with selective FGFR inhibitors, which may overcome the toxicity constraints raised by multitarget kinase inhibition, are recruiting patients with known FGFR(1-4) status based on genomic screens. Preliminary signs of antitumor activity have been demonstrated in some tumor types, including squamous cell lung carcinomas. Rational combination of targeted therapies is expected to further increase the efficacy of selective FGFR inhibitors. Herein, we discuss unsolved questions in the clinical development of these agents and suggest guidelines for management of hyperphosphatemia, a class-specific mechanism-based toxicity. In addition, we propose standardized definitions for FGFR1 and FGFR2 gene amplification based on in situ hybridization methods. Extended access to next-generation sequencing platforms will facilitate the identification of diseases in which somatic FGFR(1-4) mutations, amplifications and fusions are potentially driving cancer cell viability, further strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors.

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Molecular Profile Treatment Approach
FGFR3 R124W FGFR Inhibitor (Pan)
FGFR3 C228R FGFR3 Inhibitor
FGFR3 N540S FGFR3 Inhibitor
FGFR1 C178S FGFR Inhibitor (Pan)
FGFR3 R200C FGFR Inhibitor (Pan)
FGFR2 S372C FGFR Inhibitor (Pan)
FGFR3 S249C FGFR3 Inhibitor
FGFR2 T341P FGFR Inhibitor (Pan)
FGFR1 act mut FGFR Inhibitor (Pan)
FGFR3 R200C FGFR3 Inhibitor
FGFR2 K659N FGFR Inhibitor (Pan)
FGFR2 W290_I291delinsC FGFR Inhibitor (Pan)
FGFR3 I538V FGFR Inhibitor (Pan)
FGFR3 Y647C FGFR3 Inhibitor
FGFR3 C228R FGFR Inhibitor (Pan)
FGFR3 R669G FGFR3 Inhibitor
FGFR3 act mut FGFR Inhibitor (Pan)
FGFR2 C382R FGFR Inhibitor (Pan)
FGFR3 V555M FGFR3 Inhibitor
FGFR3 K650Q FGFR3 Inhibitor
FGFR3 N540K FGFR Inhibitor (Pan)
FGFR2 S252W FGFR Inhibitor (Pan)
FGFR3 Y647C FGFR Inhibitor (Pan)
FGFR2 D101Y FGFR Inhibitor (Pan)
FGFR2 - PPHLN1 FGFR Inhibitor (Pan)
FGFR3 K652E FGFR3 Inhibitor
FGFR2 E566A FGFR Inhibitor (Pan)
FGFR2 L618M FGFR Inhibitor (Pan)
FGFR2 K525E FGFR Inhibitor (Pan)
FGFR3 - TACC3 FGFR Inhibitor (Pan)
FGFR3 G380R FGFR3 Inhibitor
FGFR2 C342R FGFR Inhibitor (Pan)
FGFR2 M537I FGFR Inhibitor (Pan)
FGFR3 R669G FGFR Inhibitor (Pan)
FGFR2 E565A FGFR Inhibitor (Pan)
FGFR2 F276C FGFR Inhibitor (Pan)
FGFR2 D650L FGFR Inhibitor (Pan)
FGFR2 V564L FGFR Inhibitor (Pan)
FGFR2 V564I FGFR Inhibitor (Pan)
FGFR2 N549H FGFR Inhibitor (Pan)
FGFR3 K650T FGFR3 Inhibitor
FGFR3 D641G FGFR3 Inhibitor
FGFR3 S371C FGFR3 Inhibitor
FGFR3 K650M FGFR3 Inhibitor
FGFR2 M536I FGFR Inhibitor (Pan)
FGFR3 V788M FGFR3 Inhibitor
FGFR3 A391E FGFR Inhibitor (Pan)
FGFR2 R203C FGFR Inhibitor (Pan)
FGFR1 - TACC1 FGFR Inhibitor (Pan)
FGFR3 Y373C FGFR3 Inhibitor
FGFR3 - BAIAP2L1 FGFR Inhibitor (Pan)
FGFR2 N549K FGFR Inhibitor (Pan)
FGFR2 P253R FGFR Inhibitor (Pan)
FGFR1 L614V FGFR Inhibitor (Pan)
FGFR3 Y373C FGFR Inhibitor (Pan)
FGFR3 G372C FGFR3 Inhibitor
FGFR3 D641G FGFR Inhibitor (Pan)
FGFR2 S267_D273dup FGFR Inhibitor (Pan)
FGFR3 G382R FGFR3 Inhibitor
FGFR3 K650T FGFR Inhibitor (Pan)
FGFR3 K650N FGFR Inhibitor (Pan)
FGFR1 T695A FGFR Inhibitor (Pan)
FGFR3 V50I FGFR3 Inhibitor
FGFR3 R248C FGFR3 Inhibitor
FGFR1 P252S FGFR Inhibitor (Pan)
FGFR1 Y374C FGFR Inhibitor (Pan)
FGFR3 K650E FGFR Inhibitor (Pan)
FGFR2 - AHCYL1 FGFR Inhibitor (Pan)
FGFR2 V564F FGFR Inhibitor (Pan)
FGFR2 K660N FGFR Inhibitor (Pan)
FGFR3 N540S FGFR Inhibitor (Pan)
FGFR2 E566G FGFR Inhibitor (Pan)
FGFR2 N550H FGFR Inhibitor (Pan)
FGFR3 K650N FGFR3 Inhibitor
FGFR1 K656E FGFR Inhibitor (Pan)
FGFR3 D641N FGFR3 Inhibitor
FGFR3 I538V FGFR3 Inhibitor
FGFR2 - CCDC6 FGFR Inhibitor (Pan)
FGFR2 V565I FGFR Inhibitor (Pan)
FGFR2 Y376C FGFR Inhibitor (Pan)
FGFR3 G382D FGFR Inhibitor (Pan)
FGFR3 Y375C FGFR3 Inhibitor
FGFR2 - FAM76A FGFR Inhibitor (Pan)
FGFR1 P252T FGFR Inhibitor (Pan)
FGFR2 - BICC1 FGFR Inhibitor (Pan)
FGFR2 S354C FGFR Inhibitor (Pan)
FGFR2 L617V FGFR Inhibitor (Pan)
FGFR2 K641N FGFR Inhibitor (Pan)
FGFR3 G380R FGFR Inhibitor (Pan)
FGFR2 W290C FGFR Inhibitor (Pan)
FGFR2 N549T FGFR Inhibitor (Pan)
FGFR2 K642R FGFR Inhibitor (Pan)
FGFR3 A391E FGFR3 Inhibitor
FGFR2 M538I FGFR Inhibitor (Pan)
FGFR1 V561M FGFR Inhibitor (Pan)
FGFR3 V50I FGFR Inhibitor (Pan)
FGFR2 N550K FGFR Inhibitor (Pan)
FGFR3 G382D FGFR3 Inhibitor
FGFR3 act mut FGFR3 Inhibitor
FGFR2 K659E FGFR Inhibitor (Pan)
FGFR2 G663E FGFR Inhibitor (Pan)
FGFR3 amp FGFR3 Inhibitor
FGFR3 K650M FGFR Inhibitor (Pan)
FGFR1 over exp FGFR Inhibitor (Pan)
FGFR1 I544V FGFR Inhibitor (Pan)
FGFR2 K526E FGFR Inhibitor (Pan)
FGFR2 N550T FGFR Inhibitor (Pan)
FGFR2 C342Y FGFR Inhibitor (Pan)
FGFR1 C381R FGFR Inhibitor (Pan)
FGFR3 S249C FGFR Inhibitor (Pan)
FGFR3 R669Q FGFR3 Inhibitor
FGFR2 act mut FGFR Inhibitor (Pan)
FGFR2 Y375C FGFR Inhibitor (Pan)
FGFR3 R248C FGFR Inhibitor (Pan)
FGFR1 N546K FGFR Inhibitor (Pan)
FGFR2 - TACC3 FGFR Inhibitor (Pan)
FGFR3 K650E FGFR3 Inhibitor
FGFR3 D641N FGFR Inhibitor (Pan)
FGFR2 D650A FGFR Inhibitor (Pan)
FGFR3 over exp FGFR Inhibitor (Pan)
FGFR1 C379R FGFR Inhibitor (Pan)
FGFR3 Y375C FGFR Inhibitor (Pan)
FGFR3 - TACC3 FGFR3 Inhibitor
FGFR3 R669Q FGFR Inhibitor (Pan)
FGFR3 G372C FGFR Inhibitor (Pan)
FGFR2 R678G FGFR Inhibitor (Pan)
FGFR2 D650I FGFR Inhibitor (Pan)
FGFR2 E565G FGFR Inhibitor (Pan)
FGFR3 G370C FGFR Inhibitor (Pan)
FGFR3 V788M FGFR Inhibitor (Pan)
FGFR2 I548V FGFR Inhibitor (Pan)
FGFR2 K641R FGFR Inhibitor (Pan)
FGFR2 - DNM3 FGFR Inhibitor (Pan)
FGFR2 amp FGFR Inhibitor (Pan)
FGFR3 K652E FGFR Inhibitor (Pan)
FGFR3 K650Q FGFR Inhibitor (Pan)
FGFR3 V555M FGFR Inhibitor (Pan)
FGFR3 D786N FGFR3 Inhibitor
FGFR2 over exp FGFR Inhibitor (Pan)
FGFR1 amp FGFR Inhibitor (Pan)
FGFR2 I547V FGFR Inhibitor (Pan)
FGFR2 C383R FGFR Inhibitor (Pan)
FGFR3 over exp FGFR3 Inhibitor
FGFR2 N550S FGFR Inhibitor (Pan)
FGFR2 K660E FGFR Inhibitor (Pan)
FGFR3 G382R FGFR Inhibitor (Pan)
FGFR3 amp FGFR Inhibitor (Pan)
FGFR3 D786N FGFR Inhibitor (Pan)
FGFR3 S371C FGFR Inhibitor (Pan)
FGFR2 K659M FGFR Inhibitor (Pan)
FGFR3 R124W FGFR3 Inhibitor
FGFR3 N540K FGFR3 Inhibitor
FGFR3 G370C FGFR3 Inhibitor
FGFR3 - BAIAP2L1 FGFR3 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