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Dysregulated metabolism contributes to oncogenesis.


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Authors

Hirschey, Matthew D 
DeBerardinis, Ralph J 
Diehl, Anna Mae E 
Drew, Janice E 

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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Keywords

Cancer metabolism, Cancer therapy, Host metabolism, Mitochondria, Warburg, Carcinogenesis, Cell Proliferation, Cell Transformation, Neoplastic, Energy Metabolism, Epigenesis, Genetic, Humans, Metabolic Networks and Pathways, Mitochondria, Neoplasms

Journal Title

Semin Cancer Biol

Conference Name

Journal ISSN

1044-579X
1096-3650

Volume Title

35

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_UU_12022/6)
Medical Research Council (MC_U105663142)
We would like to thank Leroy Lowe for conceptualization of the Halifax project, the unnamed reviewers of this manuscript for their suggestions, and colleagues in the field who drive the science described in this review. We apologize to those whose work could not be included due to space constraints. Finally, we acknowledge all the co-authors of this review who were part of the Target Validation Team, including (in alphabetical order): Amedeo Amedei, PhD, University of Florence, Italy; Amr Amin, PhD, UAE University, United Arab Emirates; S. Salman Ashraf, PhD, UAE University, United Arab Emirates; Asfar S. Azmi, PhD, Wayne State University, Karmanos Cancer Institute, United States; Dipita Bhakta, M.Sc., PhD, VIT University (Vellore Institute of Technology), India; Alan Bisland, University of Glasgow, Glasgow, UK; Chandra S. Boosani, PhD, Creighton University, United States; Sophie Chen, PhD, Ovarian and Prostate Cancer Research Trust Laboratory, United Kingdom; Hiromasa Fujii, MD, PhD, Nara Medical University, Japan; Alexandros Georgakilas, PhD, National Technical University of Athens, Greece; Gunjan Guha, M.Sc., PhD, Assistant Professor, SASTRA University, India; Dorota Halicka, MD, PhD, New York Medical College, United States; Bill Helferich, PhD, University of Illinois at Urbana Champaign, United States; Kanya Honoki, MD, PhD, Nara Medical University, Japan; W.N. Keith, University of Glasgow, Glasgow, UK; Sulma Mohammed, DVM, PhD, Purdue University Cancer for Cancer Research, United States; Elena Niccolai, University of Florence, Italy; Somaira Nowsheen, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota, United States; Xujuan Yang, University of Illinois at Urbana Champaign, United States.