Ypoglycaemia and ketoacidaemia as a result of reduced levels of the gluconeogenic precursors. Tumor cells have been shown to alter metabolic pathways involved in glucose, glutamine and mitochondrial metabolism to generate raw materials needed for rapid cellular proliferation, maintain favorable cellular redox environments, modify cellular epigenetics and even promote and maintain oncogenic transformation. As a consequence, there has been intense scientific and clinical interest in targeting metabolic alterations that are commonly adopted by tumor cells for therapeutic purposes. In this review, we describe common metabolic alterations seen in tumor cells and discuss how these alterations are being investigated as potential targets for pharmacological intervention in preclinical and clinical settings. We also discuss some of the challenges associated with using tumor metabolism as a therapeutic target in 1235481-90-9 Cancer therapy, along with potential avenues to overcome these challenges. Keywords Tumor metabolism; aerobic glycolysis; glutamine; IDH mutations; combination therapy Therapeutic strategies for the treatment of cancer have undergone a revolution in recent years. In the past, frontline cancer therapy consisted largely of widely cytotoxic drugs that damaged both cancer cells and normal, healthy tissue. Over the past several decades, emphasis has been placed on identifying distinctive or preferential features of cancer cells to better target cancer yet spare normal cells. This has resulted in targeted therapies with higher treatment efficacy and improved patient outcomes. One recent focus in cancer research has been to exploit metabolic features of cancer cells that may separate them from normal tissue. The rationale behind this endeavor is that cancer cells, due to their rapid, sustained order Vorapaxar growth and proliferation and need to withstand hypoxia, must employ a metabolic program that Address correspondence to: Jeffrey Rathmell, DUMC Box 3813, Duke University Medical Center, Durham, NC, 27710, Phone: 919-681-1084, Fax: 919-613-6606, [email protected]. aDoctoral candidate, MS bAssociate Professor, PhD Conflicts of Interest: The authors declare no conflicts of interest. Kishton and Rathmell Page 2 deviates from the metabolic characteristics of normal, healthy tissue. The ability to target cancer metabolism may result in a therapeutic window where cancer cells are inhibited but normal healthy cells remain unaffected. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Metabolic Features of Cancer Researchers and clinicians working in cancer related fields have come to understand that cancer is a heterogeneous disease. There is tremendous variation in biology between different types of cancer, different patients with the same type of cancer, and even between different cancer cells 
in the same tumor. Cancer metabolism also exhibits considerable heterogeneity, with tumors adopting various metabolic programs that best suit a particular microenvironment. There are, however, some commonalities in cancer metabolism that are generally applicable to a significant portion of tumors. Among these common features of cancer metabolism are alterations in glucose, glutamine and mitochondrial metabolism. These commons features may allow PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19846406 for the development of novel therapeutics to target a fundamental hallmark of cancer biology. Indeed, the fundamental nature of some metabolic pathways may provide a unified target to bypass and overcome th.Ypoglycaemia and ketoacidaemia as a result of reduced levels of the gluconeogenic precursors. Tumor cells have been shown to alter metabolic pathways involved in glucose, glutamine and mitochondrial metabolism to generate raw materials needed for rapid cellular proliferation, maintain favorable cellular redox environments, modify cellular epigenetics and even promote and maintain oncogenic transformation. As a consequence, there has been intense scientific and clinical interest in targeting metabolic alterations that are commonly adopted by tumor cells for therapeutic purposes. In this review, we describe common metabolic alterations seen in tumor cells and discuss how these alterations are being investigated as potential targets for pharmacological intervention in preclinical and clinical settings. We 
also discuss some of the challenges associated with using tumor metabolism as a therapeutic target in cancer therapy, along with potential avenues to overcome these challenges. Keywords Tumor metabolism; aerobic glycolysis; glutamine; IDH mutations; combination therapy Therapeutic strategies for the treatment of cancer have undergone a revolution in recent years. In the past, frontline cancer therapy consisted largely of widely cytotoxic drugs that damaged both cancer cells and normal, healthy tissue. Over the past several decades, emphasis has been placed on identifying distinctive or preferential features of cancer cells to better target cancer yet spare normal cells. This has resulted in targeted therapies with higher treatment efficacy and improved patient outcomes. One recent focus in cancer research has been to exploit metabolic features of cancer cells that may separate them from normal tissue. The rationale behind this endeavor is that cancer cells, due to their rapid, sustained growth and proliferation and need to withstand hypoxia, must employ a metabolic program that Address correspondence to: Jeffrey Rathmell, DUMC Box 3813, Duke University Medical Center, Durham, NC, 27710, Phone: 919-681-1084, Fax: 919-613-6606, [email protected]. aDoctoral candidate, MS bAssociate Professor, PhD Conflicts of Interest: The authors declare no conflicts of interest. Kishton and Rathmell Page 2 deviates from the metabolic characteristics of normal, healthy tissue. The ability to target cancer metabolism may result in a therapeutic window where cancer cells are inhibited but normal healthy cells remain unaffected. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Metabolic Features of Cancer Researchers and clinicians working in cancer related fields have come to understand that cancer is a heterogeneous disease. There is tremendous variation in biology between different types of cancer, different patients with the same type of cancer, and even between different cancer cells in the same tumor. Cancer metabolism also exhibits considerable heterogeneity, with tumors adopting various metabolic programs that best suit a particular microenvironment. There are, however, some commonalities in cancer metabolism that are generally applicable to a significant portion of tumors. Among these common features of cancer metabolism are alterations in glucose, glutamine and mitochondrial metabolism. These commons features may allow PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19846406 for the development of novel therapeutics to target a fundamental hallmark of cancer biology. Indeed, the fundamental nature of some metabolic pathways may provide a unified target to bypass and overcome th.