Vendredi 8 Juin 2018, 14h00
Department of Molecular and Translational Medicine, University of Brescia
Summary of the work:
The fibroblast growth factor (FGF)/FGF receptor (FGFR) system plays a crucial role in cancer by affecting tumor growth, angiogenesis, drug resistance and escape from anti-angiogenic anti-vascular endothelial growth factor therapy. The soluble pattern recognition receptor long-pentraxin 3 (PTX3) acts as a multi-FGF antagonist. In a recent study we demonstrated that local and systemic delivery of human PTX3 in transgenic mice driven by the endothelial specific Tie2 promoter inhibits tumor growth, angiogenesis and metastasis in heterotopic, orthotopic and autochthonous FGF-dependent tumor models. Moreover, NMR data and pharmacophore modeling of the interaction of a minimal PTX3-derived FGF-binding pentapeptide with FGF2 were used for the identification of the first small molecule chemical (NSC12) which acts as an orally active extracellular FGF trap with significant implications in cancer therapy. We are currently characterizing the role of PTX3 expression in different types of solid and hematological tumors.
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