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Semin Cancer Biol. 2015 Dec;35 Suppl:S129-S150. doi: 10.1016/j.semcancer.2015.10.002. Epub 2015 Oct 8.

Dysregulated metabolism contributes to oncogenesis.

Author information

1
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: matthew.hirschey@duke.edu.
2
Children's Medical Center Research Institute, University of Texas - Southwestern Medical Center, Dallas, TX 75390, USA.
3
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
4
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
5
MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge, United Kingdom.
6
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA.
7
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
8
University of Maryland BioPark, KoDiscovery, Baltimore, MD 20201, USA.
9
The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
10
New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA.
11
Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14850, USA; Field of Genetics, Genomics, and Development, Cornell University, Ithaca, NY 14850, USA.
12
Andrus Gerontology Center, Division of Biogerontology, University of Southern California, Los Angeles, CA 90089, USA.
13
Department of Molecular and Integrative Physiology and Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.
14
Field of Genetics, Genomics, and Development, Cornell University, Ithaca, NY 14850, USA.
15
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.
16
MRC Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Cambridge, United Kingdom.
17
Department of Biological Chemistry and Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.
18
Laboratory of Oncology, Istituto Giannina Gaslini, Genoa, Italy.
19
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
20
Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
21
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Abstract

Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results demonstrate that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it.

KEYWORDS:

Cancer metabolism; Cancer therapy; Host metabolism; Mitochondria; Warburg

PMID:
26454069
PMCID:
PMC4656121
DOI:
10.1016/j.semcancer.2015.10.002
[Indexed for MEDLINE]
Free PMC Article

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