The NAD-ome as potential vulnerability of cancer cells
In-depth investigation of the consequences of the alterations in the NAD-ome may open novel avenues for the identification of biomarkers and personalized treatment options for Glioblastoma patients.
Cells regulate key functions using cofactors, small (bio)chemical molecules that assist in enzymatic reactions. Nicotinamide adenine dinucleotide (NAD) represents one of the most common cellular cofactors and is involved in cell signaling, bioenergy homeostasis and metabolism. Highly proliferating cancer cells show a high demand in NAD and reprogram their metabolism towards increased NAD levels. Studying and monitoring the NAD-metabolome, which this Alliance project team coined the “NAD-ome”, by a precise, sensitive and cutting-edge technology is of utmost importance and may offer potential for the identification of biomarkers and therapeutic targets in NAD-producing or -degrading pathways.
Together with the Metabolic Core Technology Platform (MCTP) the team aimed to establish a mass spectrometry (MS)-based method for robust detection of NAD and related metabolites that accumulate in the tumor cells as well as the tumor microenvironment. They developed an MS-based technology to monitor NAD and a broad range of related metabolites. The NAD profiling technology (NAD ProTec) comprised 33 different NAD-related compounds. The team established and optimized NAD ProTec using four different glioblastoma (GB) cells, cultured in the absence and presence of NAD precursors. They validated the NAD ProTec results using a plate reader-based enzymatic, colorimetric NAD cycling assay. NAD ProTec identified conditions that drive the formation of NAD in GB cells. In-depth investigation of the consequences of these alterations may open novel avenues for the identification of biomarkers and personalized treatment options for GB patients.