[Frontiers In Bioscience, Landmark, 22, 1221-1246, March 1, 2017]

Racial disparity in metabolic regulation of cancer

Kuldeep S. Attri1, Divya Murthy1, Pankaj K. Singh1,2,3,4

1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA, 2Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA, 3Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA, 4Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA


1. Abstract
2. Introduction
3. Racial disparity in incidence, mortality and risk factors in cancer
4. Metabolic reprogramming in cancer
5. Enzymatic gene mutations as mediators of metabolic rewiring
6. Mutational control of metabolic regulations
6.1. Oncogene-directed metabolic rewiring
6.2. Signaling pathway-mediated metabolic reprogramming
6.2.1. EGFR signaling in cancer
6.2.2. PI3/AKT signaling
6.3. Metabolic reprogramming mediated by the tumor microenvironment
7. Metabolic gene mutations as differential predictors of cancer risk
8. Metabolic profiles as discriminators of cancer risk in different racial groups
9. Racial disparity in genetic regulation of cancer prognosis and therapy
10. Summary and perspective
11. Acknowledgements
12. References


Genetic mutations and metabolic reprogramming are two key hallmarks of cancer, required for proliferation, invasion, and metastasis of the disease. While genetic mutations, whether inherited or acquired, are critical for the initiation of tumor development, metabolic reprogramming is an effector mechanism imperative for adaptational transition during the progression of cancer. Recent findings in the literature emphasize the significance of molecular cross-talk between these two cellular processes in regulating signaling and differentiation of cancer cells. Genome-wide sequencing analyses of cancer genomes have highlighted the association of various genic mutations in predicting cancer risk and survival. Oncogenic mutational frequency is heterogeneously distributed among various cancer types in different populations, resulting in varying susceptibility to cancer risk. In this review, we explore and discuss the role of genetic mutations in metabolic enzymes and metabolic oncoregulators to stratify cancer risk in persons of different racial backgrounds.


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Key Words: Cancer, Metabolism, Race, Ethnic, Mutation, Oncogene, Tumor suppressor, Oncometabolite

Send correspondence to: Pankaj K. Singh, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, Tel: 402-559-2726, Fax: 402-559-2813, E-mail: pankaj.singh@unmc.edu