98 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)S129-S150
JournalSeminars in Cancer Biology
Volume35
DOIs
StatePublished - Dec 1 2015

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Carcinogenesis
Neoplasms
Metabolic Networks and Pathways
Epigenomics
Tumor Suppressor Genes
Oncogenes
Cell Proliferation
Food
Mutation
Enzymes
Growth
Research

Keywords

  • Cancer metabolism
  • Cancer therapy
  • Host metabolism
  • Mitochondria
  • Warburg

ASJC Scopus subject areas

  • Cancer Research

Cite this

Dysregulated metabolism contributes to oncogenesis. / Target Validation Team.

In: Seminars in Cancer Biology, Vol. 35, 01.12.2015, p. S129-S150.

Research output: Contribution to journalReview article

Target Validation Team. / Dysregulated metabolism contributes to oncogenesis. In: Seminars in Cancer Biology. 2015 ; Vol. 35. pp. S129-S150.
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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.",
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author = "{Target Validation Team} and Hirschey, {Matthew D.} and DeBerardinis, {Ralph J.} and Diehl, {Anna Mae E} and Drew, {Janice E.} and Christian Frezza and Green, {Michelle F.} and Jones, {Lee W.} and Ko, {Young H.} and Anne Le and Lea, {Michael A.} and Locasale, {Jason W.} and Longo, {Valter D.} and Lyssiotis, {Costas A.} and Eoin McDonnell and Mahya Mehrmohamadi and Gregory Michelotti and Vinayak Muralidhar and Murphy, {Michael P.} and Pedersen, {Peter L.} and Brad Poore and Lizzia Raffaghello and Rathmell, {Jeffrey C.} and Sharanya Sivanand and {Vander Heiden}, {Matthew G.} and Wellen, {Kathryn E.} and Amedeo Amedei and Amr Amin and {Salman Ashraf}, S. and Azmi, {Asfar S.} and Dipita Bhakta and Alan Bisland and Boosani, {Chandra S.} and Sophie Chen and Hiromasa Fujii and Alexandros Georgakilas and Gunjan Guha and Dorota Halicka and Bill Helferich and Kanya Honoki and Keith, {W. N.} and Sulma Mohammed and Elena Niccolai and Somaira Nowsheen and Xujuan Yang",
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AU - Green, Michelle F.

AU - Jones, Lee W.

AU - Ko, Young H.

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AU - Locasale, Jason W.

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AU - Rathmell, Jeffrey C.

AU - Sivanand, Sharanya

AU - Vander Heiden, Matthew G.

AU - Wellen, Kathryn E.

AU - Amedei, Amedeo

AU - Amin, Amr

AU - Salman Ashraf, S.

AU - Azmi, Asfar S.

AU - Bhakta, Dipita

AU - Bisland, Alan

AU - Boosani, Chandra S.

AU - Chen, Sophie

AU - Fujii, Hiromasa

AU - Georgakilas, Alexandros

AU - Guha, Gunjan

AU - Halicka, Dorota

AU - Helferich, Bill

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KW - Cancer therapy

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