FGF Program

Fibroblast growth factors, or FGFs, and their receptors, FGFR1-4, represent a signaling network that plays important roles in the regulation of cell growth, survival, differentiation and angiogenesis. Through its HRP, AVEO has identified FGF ligands and receptors as powerful drivers of tumor growth in a variety of tumor models and implicated the activation of the pathway in tumor development. Increasing amounts of human genetic and genomic data also point to the alteration of this pathway in the development of a number of different types of human cancers.

 

Certain FGF ligands have been shown to have pro-angiogenic activity and may act synergistically with vascular endothelial growth factor (VEGF) to amplify tumor angiogenesis. The upregulation of FGF pathway activity in response to anti-VEGF therapy is thought to play an important role in the development of resistance to VEGF inhibition, suggesting that the combination of FGF and VEGF pathway inhibitors may add to the benefits achievable by targeting VEGF alone.

 

The goal of AVEO’s ongoing drug discovery efforts is to identify specific FGFR1, FGFR2, FGFR3 and FGFR4 inhibitory antibodies that prevent activation of these receptors. The activity of candidate antibodies will be evaluated in specific target-driven tumor models created using the HRP.

 

Findings from AVEO’s work on the FGFR pathway, which strongly support the belief that FGFR2 plays an essential role in the initiation and/or maintenance of human cancers harboring FGFR2 amplification, were recently presented at the 2010 EORTC-NCI-AACR Symposium in Berlin.