The CCND1-FGF19-FGF4-FGF3 gene cluster in human chromosome 11q13 is amplified in breast cancer, squamous cell carcinoma of head and neck, and bladder tumors, and is also translocated in parathyroid tumors and B-cell lymphoma.
Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase.
When qPCR-identified amplifications in FGFR1, FGFR2, or FGF3 were grouped to define an FGF pathway-amplified breast cancer in HR-positive patients, the mean reduction in target lesions was 21.1% compared with a 12.0% increase in patients who did not present with FGF pathway-amplified breast cancer.
Therefore, in this study, locus 11q13 and FGF3 gene (11q13) function were investigated in a radiation and estrogen breast cancer model induced by high-LET (α-particle) radiation and estrogen exposure.
Taken together, these results demonstrated that the peptide FP16, acting as an FGF3 antagonist, is a promising therapeutic agent for the treatment of breast cancer.