FGFR2 gene encodes
FGFR2b in epithelial cells, and
FGFR2c in mesenchymal cells.
FGFR2b is a high affinity receptor for
FGF1, FGF3, FGF7, FGF10 and FGF22, while
FGFR2c for
FGF1,
FGF2, FGF4, FGF6, FGF9, FGF16 and FGF20. Here genomics and genetics of FGFR2, and
therapeutics targeted to FGFR2 will be reviewed. Single nucleotide polymorphisms (SNPs) of FGFR2 are associated with increased risk of
breast cancer. Gene amplification or missense mutation of FGFR2 occurs in
gastric cancer,
lung cancer,
breast cancer,
ovarian cancer, and
endometrial cancer. Genetic alterations of FGFR2 induce aberrant FGFR2 signaling activation due to release of FGFR2 from autoinhibition, or creation of FGF signaling autocrine loop. Class switch of
FGFR2b to
FGFR2c is associated with more malignant phenotype. FGF and canonical WNT signals synergize during mammary
carcinogenesis, but counteract during osteogenesis and adipogenesis. Among
PD173074,
SU5402, and
AZD2171 functioning as FGFR inhibitors,
AZD2171 is the most promising anti-
cancer drug.
Cancer genomics and genetics are utilized to predict
cancer-driving pathway for therapeutic optimization. FGFR2ome is defined as a complete data set of SNP, copy number variation (CNV), missense mutation, gene amplification, and predominant
isoform of FGFR2. FGFR2ome analyses in patients with several
tumor types among various populations should be carried out to establish integrative database of FGFR2 for the rational clinical application of FGFR2-targeted
cancer therapy.