Yetis Gultekin1, Matthew G. Vander Heiden1,2 and Evan C. Lien3 1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA 2Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA 3Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, Michigan 49503, USA Correspondence: mvhmit.edu

Altered metabolism is a hallmark of cancer that reflects the increased energetic and biosynthetic demands of proliferating cancer cells. Accumulating evidence suggests that many aspects of tumor metabolism in vivo differ from those of cancer cells in culture, and that the tumor microenvironment plays a major role in driving these differences. Apart from cancer cells, tumors are composed of diverse cell types including vascular cells, fibroblasts, and immune cells. Nutrient sharing and competition between different cell types and access to nutrients in tumor tissue are not well modeled in standard monoculture systems. Tumors can also interact with whole body metabolism and share nutrients with peripheral tissues such as fat and muscle. Hence, studying some aspects of cancer metabolism in mouse models is useful for examining the complex metabolic interactions between cells and tissues. In this article, we discuss how advances in mouse modeling have enabled studies of tumor metabolism in vivo, providing insight into metabolic factors that influence cancer cell behavior in the physiological context of a whole organism. These studies are providing insight into how to leverage altered cancer metabolism for improved therapy.