Author/Authors :
Wang, Wanqin Department of Cancer Systems Imaging - The University of Texas MD Anderson Cancer Center - Houston, USA , Zhao, Jun Department of Cancer Systems Imaging - The University of Texas MD Anderson Cancer Center - Houston, USA , Wen, Xiaoxia Department of Cancer Systems Imaging - The University of Texas MD Anderson Cancer Center - Houston, USA , Chun-Jen Lin, Curtis Department of Systems Biology - The University of Texas MD Anderson Cancer Center - Houston, USA , Li, Junjie Department of Cancer Systems Imaging - The University of Texas MD Anderson Cancer Center - Houston, USA , Huang, Qian Department of Cancer Systems Imaging - The University of Texas MD Anderson Cancer Center - Houston, USA , Yu, Yongqiang Department of Radiology - The 1st Affiliated Hospital of Anhui Medical University - Hefei, Anhui, China , Lin, Shiaw-Yih Department of Systems Biology - The University of Texas MD Anderson Cancer Center - Houston, USA , Li, Chun Department of Cancer Systems Imaging - The University of Texas MD Anderson Cancer Center - Houston, USA
Abstract :
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.
Keywords :
AXL , PET/CT , HSP90 , TNBC
