METABOLIGHT SIGNED

Project "METABOLIGHT" data sheet

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 Project objective

'Recent investigations revealed that cancer tissue possesses several important metabolic features, such as differential utilization of many essential metabolites. This phenomenon is now referred to as 'metabolic reprogramming' and is known to be required for malignant transformation, tumor development, invasion and metastasis. Its complex and dynamic nature has been recognized as one of the major challenges for effective cancer treatment. Therefore, a better understanding of metabolic dependencies in specific tumor types can provide a path for improved cancer treatments.

However, no efficient methodologies currently exist that allow noninvasive imaging and quantification of the uptake of essential metabolites in animal models of disease. Current strategies rely on either nuclear imaging techniques such as PET/SPECT/MRI or endpoint ex vivo quantification of metabolites (ex. MS). All of these methods have significant limitations, resulting in a lack of understanding of tumor metabolism and, consequently, poor predictability and efficacy of cancer therapies.

To address the unmet need for nutrient uptake imaging tools, we propose to develop a novel platform based on a combination of versatile “click” chemistry reactions with noninvasive, ultrasensitive bioluminescent imaging techniques. The applications of the novel platform will focus on tumor uptake measurements of glucose, fatty acids, amino acids, and nucleosides previously reported to play important roles in cancer metabolism. We will then use this platform to investigate the metabolic reprogramming of different liver cancers, which may lead to the generation of novel, effective treatments; therefore, this novel platform has high clinical applicability. Due to its versatile nature, application of the platform can be expended to studies of many other important human pathologies in which changes in metabolism play a key role, such as diabetes, neurodegenerative diseases, nonalcoholic steatohepatitis, and many others'