Abstract #0058

Effect of the HIF Pathway Inhibitor NSC-134754 on Glucose Metabolism

Lauren C. J. Baker¹, Yuen-Li Chung¹, Jessica K. Boult¹, Margaret A. Ashcroft², Simon P. Robinson¹

¹CRUK & EPSRC Cancer Imaging Centre, the Institute of Cancer Research & Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom; ²University College London, United Kingdom

Hypoxia-inducible factor (HIF) pathway inhibitors are an emerging class of therapeutics, whose precise mechanism of action is unclear. In this study, we examined the metabolic effects of NSC-134754, a small molecule inhibitor of the HIF pathway. Firstly, we show that NSC-134754 downregulates both the expression and distribution of glucose transporter 1, a downstream target of HIF-1. Secondly, magnetic resonance spectroscopy reveals a unique metabolic profile of the actions of NSC-134754 on cellular metabolism. Finally, we demonstrate that effects on glucose transport in vitro with NSC-134754 are reproduced in vivo in an orthotopic model of prostate cancer.