Evaluating Acute Response to the Novel HIF Inhibitor NSC-134754 in an Orthotopic Prostate Tumour Model by MRI

Lauren CJ Baker¹, Simon Walker-Samuel¹, Jessica K. Boult¹, Yann Jamin¹, Margaret A. Ashcroft², Simon P. Robinson¹

Hypoxia-inducible factor-1 (HIF-1) is recognised as a key player in tumour cell adaptation to the hypoxic microenvironment. Putative HIF inhibitors are currently under investigation, and methods for assessing tumour response pursued. NSC-134754 was recently identified as a novel HIF-1 inhibitor which has efficacy in vivo. In this study, and for the first time, MR imaging biomarkers were used to assess acute response to NSC-134754 in vivo. Alterations in Ktrans , ADC and baseline R2* were apparent, though not significant. Given the complexity of the HIF pathway it is proposed that novel HIF inhibitors exhibit distinct, tumour-specific, time-dependent modes of effect.