ReviewsAlternative Fuels for Cancer CellsKeenan, Melissa M. BS*†; Chi, Jen-Tsan MD, PhD*†Author Information From the *Department of Molecular Genetics and Microbiology and †Center for Genomic and Computational Biology, School of Medicine, Duke University, Durham, NC. Support was provided by the National Institutes of Health (CA125618, CA106520, F31 CA180610-02) and the Department of Defense (W81XWH-12-1-0148, W81XWH-14-1-0309). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Reprints: Jen-Tsan Chi, MD, PhD, Department of Molecular Genetics and Microbiology, Duke Center for Genomic and Computational Biology, CIEMAS 2177A, DUMC 3382, Duke Medical Center, Durham, NC 27708. E-mail: [email protected]. The Cancer Journal: March/April 2015 - Volume 21 - Issue 2 - p 49-55 doi: 10.1097/PPO.0000000000000104 Buy Metrics Abstract Tumor metabolism is significantly altered to support the various metabolic needs of tumor cells. The most prominent change is the increased tumor glycolysis that leads to increased glucose uptake and utilization. However, it has become obvious that many nonglucose nutrients, such as amino acids, lactate, acetate, and macromolecules, can serve as alternative fuels for cancer cells. This knowledge reveals an unexpected flexibility and evolutionarily conserved model in which cancer cells uptake nutrients from their external environment to fulfill their necessary energetic needs. Tumor cells may have evolved the ability to utilize different carbon sources because of the limited supply of nutrients in their microenvironment, which can be driven by oncogenic mutations or tumor microenvironmental stresses. In certain cases, these factors permanently alter the tumor cells’ metabolism, causing certain nutrients to become indispensable and thus creating opportunities for therapeutic intervention to eradicate tumors by their metabolic vulnerabilities. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.