Abstract
Cancer is a prime example of a disease process in which carcinogenic and metabolic changes are intertwined to promote cell survival and growth. One approach to unravel this complex relationship is by studying rare, monogenic disorders caused by mutations in genes encoding metabolic enzymes or regulators. There are hundreds of these diseases, most of which manifest in childhood and are collectively termed 'inborn errors of metabolism' (IEMs). Several IEMs demonstrate the consequences of chronic, systemic loss of a particular metabolic activity that can result in malignancy. In this Opinion article, we present a conceptual categorization of IEMs associated with cancer and discuss how assessment of these rare diseases might inform us about the biological foundations of common types of cancer and opportunities for cancer diagnosis and therapy.
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Acknowledgements
The authors thank D. Valle and B. Lee for sharing their insights on the mechanisms by which IEMs lead to tissue dysfunction. R.J.D. is the Joel B. Steinberg Chair of Pediatrics at the University of Texas Southwestern Medical Center and is supported by grants from the US National Institutes of Health (CA157996) and the Cancer Prevention and Research Institute of Texas (RP130272). He is on the scientific advisory boards of Agios Pharmaceuticals and Peloton Therapeutics. A.E. is the incumbent Leah Omenn Career Development Chair and is supported by research grants from the European research program (CIG618113, ERC614204), the Israel Science Foundation (1343/13; 1952/13) and the Minerva grant award (711730). A.E. received additional support from the Adelis Foundation, the Henry S. and Anne S. Reich Research Fund, the Dukler Fund for Cancer Research, the Paul Sparr Foundation, the Saul and Theresa Esman Foundation, Joseph Piko Baruch and the estate of Fannie Sherr.
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R.J.D. is a member of the Scientific Advisory Board of Agios Pharmaceuticals and Peloton Therapeutics, two companies interested in cancer metabolism. A.E. declares no competing interests.
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Erez, A., DeBerardinis, R. Metabolic dysregulation in monogenic disorders and cancer — finding method in madness. Nat Rev Cancer 15, 440–448 (2015). https://doi.org/10.1038/nrc3949
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