Evaluation of: Turner N, Pearson A, Sharpe R et al. FGFR1 amplification drives endocrine
therapy resistance and is a therapeutic target in
breast cancer.
Cancer Res. 70(5), 2085-2094 (2010).
FGF receptor (FGFR) family members are aberrantly activated during
carcinogenesis due to gene amplification,
chromosomal translocation and missense mutation. FGFR1 is preferentially amplified in
estrogen receptor-positive
breast cancer, whereas FGFR2 is amplified in
triple-negative breast cancer and diffuse-type
gastric cancer. Gene amplification of FGFRs results in
ligand-independent FGFR signaling to RAS-ERK, PI3K-AKT and JAK-STAT cascades due to the overexpression of wild-type or C-terminally deleted FGFRs.
Cediranib,
TKI258,
Ki23057,
MK-2461 and
brivanib are broad-range
tyrosine kinase inhibitors targeting FGFRs and other receptors. Clinical application of small-molecule FGFR inhibitors could improve the prognosis of FGFR-driven
cancer patients. Diagnostic detection of
tumors with FGFR genetic alterations in primary lesion, peritoneal effusion,
pleural effusion and bone marrow is necessary to select patients for FGFR-targeted
therapeutics.