Cancer remains one of the leading causes of death globally and no efficient treatments currently exist for many cancer types. Recent investigations revealed that cancer possesses several important metabolic features, such as differential utilization of many essential metabolites. These phenomena are collectively referred to as "metabolic reprogramming", which is now recognized as one of the important hallmarks of cancer. These metabolic alterations often promote tumorigenesis but also provide opportunities for potential anti-cancer therapies based on potent metabolic inhibitors recently developed. However, no efficient methodologies currently exist that allow noninvasive imaging and quantification of the uptake of essential metabolites in animal models of disease. Thus, our knowledge of which cancers depend on which specific nutrient remains very limited. This significantly hampers the development of efficient drug combinations for the treatment of cancer. Therefore, better understanding of cancer-specific exogenous metabolite dependencies in various types of tumors may lead to identification of improved cancer treatments.
To address the unmet need for nutrient uptake imaging tools, we propose to develop a novel METABOLIGHT imaging platform based on ultrasensitive bioluminescent imaging. The applications of the novel platform will focus on the development of probes for various metabolites previously reported to play important roles in cancer metabolism. We will then use this platform to investigate the metabolic reprogramming of two different liver cancers, which may lead to the generation of novel, effective treatments of this deadly disease.
