Probing Cancer Metabolism Using Isotope Tracers

Tumors and proliferating tissues exhibit a unique metabolic profile which fuels cell growth and division.  As a result, there is a renewed interest in exploiting metabolic pathways for the therapeutic treatment of cancer.  In conjunction with established techniques for analyzing cell signaling and transcriptional regulation, we have applied stable isotope tracers, chromatography coupled to mass spectrometry, and computational tools for flux analysis to identify activated metabolic pathways in transformed cells.  Together, these tools offer researchers the ability to quantitatively characterize metabolism in unprecedented detail.  To highlight the utility of this approach I will describe results in three systems of cellular transformation: lipogenesis in renal cell carcinoma, metabolic transformation upon K-ras mutation, and overexpression of the ErbB2 oncogene in breast cancer.  Our findings demonstrate the unique capabilities of isotopic tracers and metabolic flux analysis (MFA) to uncover the regulation of central carbon metabolism and substrate utilization by oncogenes and tumor suppressors.  Moving forward, application of such methods to model systems of cancer is of paramount importance as we attempt to mitigate tumor growth by targeting metabolic pathways.