Abstract

Reprogramming metabolism is a hallmark of malignancy. Understanding the metabolic transitions that accompany transformation may produce translatable insights for cancer diagnosis and treatment. We study tumor cell metabolism in culture, mouse models, and human patients. By analyzing metabolism in cultured cells, we have identified a finite set of cell-autonomous metabolic platforms that support survival and growth. These platforms are easily distinguished from each other by analyzing the contribution of glucose and glutamine to the tricarboxylic acid cycle. We have also developed methods to probe metabolism in models that more faithfully recapitulate cell growth in vivo, and to probe metabolism directly in live tumors. This has revealed utilization of many of the same activities observed in conventional culture, as well as striking differences that presumably reflect the effect of the microenvironment. Ongoing work will develop methods to translate these findings into novel imaging approaches to diagnose and monitor cancer.