title: Cancer metabolism: a therapeutic perspective.
abstract: Awareness that the metabolic phenotype of cells within tumours is heterogeneous - and distinct from that of their normal counterparts - is growing. In general, tumour cells metabolize glucose, lactate, pyruvate, hydroxybutyrate, acetate, glutamine, and fatty acids at much higher rates than their nontumour equivalents; however, the metabolic ecology of tumours is complex because they contain multiple metabolic compartments, which are linked by the transfer of these catabolites. This metabolic variability and flexibility enables tumour cells to generate ATP as an energy source, while maintaining the reduction-oxidation (redox) balance and committing resources to biosynthesis - processes that are essential for cell survival, growth, and proliferation. Importantly, experimental evidence indicates that metabolic coupling between cell populations with different, complementary metabolic profiles can induce cancer progression. Thus, targeting the metabolic differences between tumour and normal cells holds promise as a novel anticancer strategy. In this Review, we discuss how cancer cells reprogramme their metabolism and that of other cells within the tumour microenvironment in order to survive and propagate, thus driving disease progression; in particular, we highlight potential metabolic vulnerabilities that might be targeted therapeutically.
authors.affiliation: The Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Ubaldo E
authors.initials: UE
authors.lastname: Martinez-Outschoorn
authors.affiliation: The Breast Cancer Now Manchester Research Unit, Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.|The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Peiris-Pagés
authors.affiliation: The Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.affiliation: The Breast Cancer Now Manchester Research Unit, Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.|The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.|School of Environment and Life Sciences, University of Salford, Cockcroft Building, Salford M5 4WT, UK.
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.affiliation: The Breast Cancer Now Manchester Research Unit, Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.|The Manchester Centre for Cellular Metabolism (MCCM), Institute of Cancer Sciences, Cancer Research UK Manchester Institute, University of Manchester, Paterson Building, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000222:Adaptation, Physiological; D000596:Amino Acids / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D001343:Autophagy / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D057890:Epigenomics; D005227:Fatty Acids / Q000378:metabolism; D018740:Genetic Heterogeneity; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis; D008928:Mitochondria / Q000187:drug effects; D000069396:Mitochondrial Ribosomes / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009696:Nucleic Acids / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D000975:Antioxidants; D001786:Blood Glucose; D005227:Fatty Acids; D007657:Ketone Bodies; D008055:Lipids; D009696:Nucleic Acids; D014157:Transcription Factors; D005973:Glutamine; D019344:Lactic Acid; D018698:Glutamic Acid; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases