The Precision Medicine Initiative has driven the need for targeted therapy development to increase cancer patient survival. Due to this initiative, developing enhanced methods for measuring the accuracy and specificity of lead compound delivery is critical for moving these compounds through preclinical studies at a more efficient rate. The Experimental and Preclinical Imaging Core at the University of Kansas (epicore.ku.edu) is developing reporter constructs to assist in validating lead compound inhibition of oncogenic targets. Our lentiviral reporter constructs are used to establish stable cell lines that can be used either in vitro or in vivo to ensure optimal target inhibition. Our constructs include promoter reporters as well as 3’ untranslated-region (UTR) reporters to measure either changes in mRNA stabilization or translation by RNA-binding proteins or microRNA target validation. Our goal is to provide reporter constructs that will enable industry and academic institutions to ensure optimal inhibition of signaling pathways targeted by their lead compounds or microRNA-based therapies. Currently, we are constructing stable cancer cell lines that express near-infrared proteins, such as iRFP670, for measuring primary tumor and metastatic growth in vivo. In comparison to luciferase-expressing cell lines, we have found that cells expressing iRFP670 provided a more robust signal and were easier to image without the need for injecting a substrate. New promoter and 3’UTR reporters are being developed using iRFP670 and will be tested in vivo.
Citation Format: Rebecca T. Marquez, Liang Xu, Experimental and Preclinical Imaging Core. Reporter systems to measure dynamics and specificity of targeted cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4193.