MicroPET/CT Imaging of AXL Downregulation by HSP90 Inhibition in Triple-Negative Breast Cancer.
Wanqin WangJun ZhaoXiaoxia WenCurtis Chun-Jen LinJunjie LiQian HuangYongqiang YuShiaw-Yih LinChun LiPublished in: Contrast media & molecular imaging (2017)
AXL receptor tyrosine kinase is overexpressed in a number of solid tumor types including triple-negative breast cancer (TNBC). AXL is considered an important regulator of epithelial-to-mesenchymal transition (EMT) and a potential therapeutic target for TNBC. In this work, we used microPET/CT with 64Cu-labeled anti-human AXL antibody (64Cu-anti-hAXL) to noninvasively interrogate the degradation of AXL in vivo in response to 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent inhibitor of HSP90. 17-AAG treatment caused significant decline in AXL expression in orthotopic TNBC MDA-MB-231 tumors, inhibited EMT, and delayed tumor growth in vivo, resulting in significant reduction in tumor uptake of 64Cu-anti-hAXL as clearly visualized by microPET/CT. Our data indicate that 64Cu-anti-hAXL can be useful for monitoring anti-AXL therapies and for assessing inhibition of HSP90 molecular chaperone using AXL as a molecular surrogate.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- heat shock protein
- computed tomography
- dual energy
- heat shock
- epithelial mesenchymal transition
- heat stress
- endothelial cells
- contrast enhanced
- high resolution
- magnetic resonance imaging
- risk assessment
- electronic health record
- machine learning
- transcription factor
- signaling pathway
- metal organic framework
- oxidative stress
- aqueous solution
- single molecule
- cell death
- mass spectrometry
- combination therapy
- replacement therapy
- deep learning
- smoking cessation