Comparisons of the Efficacy of a Jak1/2 Inhibitor (AZD1480) with a VEGF Signaling Inhibitor (Cediranib) and Sham Treatments in Mouse Tumors Using DCE-MRI, DW-MRI, and Histology

摘要: Jak1/2 inhibition suppresses STAT3 phosphorylation that is characteristic of many cancers. Activated promotes the transcription factors enhance tumor growth, survival, and angiogenesis. AZD1480 a novel small molecule inhibitor Jak1/2, which key mediator activation. This study examined use diffusion-weighted (DW) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) biomarkers in assessing early response to AZD1480. Cediranib (AZD2171), vascular endothelial growth factor signaling inhibitor, was used as comparator. Thirty mice were injected with Calu-6 lung cancer cells randomized into three treatment groups: AZD1480, cediranib, sham. DW-MRI DCE-MRI protocols performed at baseline days 3 5 after treatment. The percent change from measurements for K trans , ADC v e calculated compared hematoxylin eosin (H&E), CD31, cParp, Ki-67 histology data. Decreases 29% ( P occurred group, but significant increase demonstrated (63%, not pharmacodynamic biomarker these time points.