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Abstract #0933

Tumour vascular response to the FGFR inhibitor derazantinib assessed using susceptibility-contrast MRI with ferumoxytol

Jessica K.R. Boult1, Mahmoud El Shemerly2, Felix Bachmann2, Laurenz Kellenberger2, Heidi Lane2, Paul McSheehy2, and Simon P. Robinson1
1The Institute of Cancer Research, Sutton, United Kingdom, 2Basilea Pharmaceutica International Ltd, Basel 4005, Switzerland

Derazantinib (DZB), a FGFR inhibitor, has displayed potential anti-angiogenic effects in biochemical assays. In this study, we used in vitro and in vivo assays to explore this activity. Proliferation of human umbilical vein endothelial cells, their pVEGFR expression and downstream signalling, and vascular permeability in mouse skin are dose-dependently supressed by DZB. Susceptibility-contrast MRI using ferumoxytol demonstrated a reduction in fractional blood volume in subcutaneous colorectal cancer xenografts treated with DZB for 48h. This anti-angiogenic effect may be a relevant component of the activity of DZB in tumours bearing FGFR aberrations and may facilitate clinical activity against other solid tumours.

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