Advanced, metastatic stages of breast cancer are associated with high morbidity and mortality, and there is a need to establish a proof-of-concept for novel compounds that can change this scheme. Fibroblast growth factors and their receptors (FGFRs) are altered in about 18% of breast cancers, resulting in malignant growth and resistance to conventional therapies. During the past few years many compounds inhibiting the activity of FGFRs have been discovered but not yet approved for breast cancer.

In this study, the effects of pharmacological inhibition of FGFRs by FGFRselective and non-selective inhibitors on proliferation, apoptosis, migration, invasion and angiogenesis were evaluated by different in vitro and in vivo models, and in ex vivo explant cultures using clinical breast cancer tissue specimens. FGFR1 was a major regulator of breast cancer growth. FGFR selective inhibitors were most effective in FGFR-amplified cells. FGFR inhibitors decreased proliferation of breast cancer cells, which was the major cause of growth inhibition.Migration and invasion were also inhibited, and induction of apoptosis was observed in certain experimental models. FGFR inhibitors decreased tumor growth in subcutaneous models, and also in a model mimicking growth of bone metastases in vivo. FGFR inhibitors did not have any harmful effects on healthy bone or on boneforming osteoblasts.

In conclusion, FGFR inhibitors showed many anti-tumor effects in breast cancer. Many of these compounds are currently being evaluated in clinical trials.