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Molecular imaging of redox processes in cancer (ImagingRedox)
Date du début: 1 mars 2014, Date de fin: 28 févr. 2018 PROJET  TERMINÉ 

Background:The ability of cancer cells to survive extreme levels of oxidative stress, an imbalance of free radicals and antioxidants, plays a role in disease aggressiveness. However, there are currently no methods to image the spatial distribution of redox state in the clinic and few preclinical methods have the potential for translation. Our long term goal is to develop sensitive and specific imaging tools with which to study how redox processes contribute to cancer drug resistance, with a view to translating these results into clinical applications.Aims:We aim to explore the hypothesis that the ability of cancer cells to detoxify free radicals is linked to their capacity to evade cell death during therapy. We will perform our studies to test this hypothesis first using live cell microscopy, then through imaging in small animal models.Methods:Existing methods for measuring redox state in live cells, including fluorescence and Raman microscopy, will be studied during modulation of the external environment and derivation of drug resistance. These readouts will be compared to classical biochemical assays of oxidative stress upon cell harvest. A low cost, high sensitivity instrument will then be developed to image these same contrast mechanisms through endoscopy in colorectal cancer mouse models. Finally, a novel “smart” contrast agent concept will be explored to enable deep tissue redox imaging, using both fluorescence endoscopy and photoacoustic tomography.How the results of this research will be used:If elevated antioxidant capacity is causative in the development of drug resistance, the results of this work will provide new strategies for detecting relapse and may aid clinical trials of therapies to target this adaptation. Ultimately, the Marie Curie Career Integration Grant will enable the researcher to establish this novel research area at the University of Cambridge, by strengthening existing collaborations and developing new links within the EU.