Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets

Abstract

Cancer treatments are increasingly focusing on the molecular mechanisms underlying the oncogenic processes present in tumors of individual patients. Fibroblast growth factor receptors (FGFRs) are among the many molecules that are involved in oncogenesis and are currently under investigation for their potential as drug targets in breast cancer patients. These receptor tyrosine kinases play a role in several processes including proliferation, angiogenesis, and migration. Alterations in these basal processes can contribute to the development and progression of tumors. Among breast cancer patients, several subgroups have been shown to harbor genetic aberrations in FGFRs, including amplifications of FGFR1, FGFR2, and FGFR4 and mutations in FGFR2 and FGFR4. Here, we review in vitro and in vivo models that have partly elucidated the molecular implications of these different genetic aberrations, the resulting tumor characteristics, and the potential of FGFRs as therapeutic targets for breast cancer treatment.

ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming

“…Instead, other genes showed more striking increases in H3K4me3 near the transcription start site, such as the mesenchymal marker N-cadherin, the axon guidance pathway markers SEMA3A and SEMA3D, and the stem cell markers SOX9 and FGFR2, as examples. FGFR2 has important roles in embryonic development and is a breast cancer susceptibility gene (32). SOX9 is an embryonic transcription factor and key regulator of the mammary stem cell Figure 18).…”

Signaling pathways influencing tumor microenvironment and their exploitation for targeted drug delivery

“…Being a crucial signaling for basic processes such as proliferation, survival, angiogenesis, and migration, deregulated FGF signaling can contribute to the development and progression of tumors [16]. FGFR signaling is altered in many cancers including benign skin tumors [17], prostate [18], bladder, and breast cancers [19][20][21]. Breast cancer cells have been reported to overexpress FGFR1, 2, 4 and display mutations in FGFR2 and 4 [21].…”

“…FGFR signaling is altered in many cancers including benign skin tumors [17], prostate [18], bladder, and breast cancers [19][20][21]. Breast cancer cells have been reported to overexpress FGFR1, 2, 4 and display mutations in FGFR2 and 4 [21]. Moreover, emerging data suggest that in addition to the known functions of FGF signaling in promoting tumor cell proliferation and survival, FGF signaling might also regulate EMT [22], tumor metastasis and lymphangiogenesis in a vascular endothelial growth factor-C (VEGF-C)-dependent mechanism [23].…”

The expression of fibroblast growth factor receptors during early bovine conceptus development and pharmacological analysis of their actions on trophoblast growth in vitro

“…In the human placenta, FGFR4 mRNA localizes to several trophoblast cell types at the decidualtrophoblast border, suggesting a role in maintaining this interface (Anteby et al 2005). FGFR4 is also needed during neural development and is linked with various cancers in several species (Marchal et al 2009, Ota et al 2010, Tenhagen et al 2012.…”