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Abstract #4191

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

1The Institute of Cancer Research, Sutton, Surrey, UK; 2Division of Medicine, University College, London, UK

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.