Metabolic dysregulation in monogenic disorders and cancer - finding method in madness

Nat Rev Cancer. 2015 Jul;15(7):440-8. doi: 10.1038/nrc3949. Epub 2015 Jun 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Glycolysis
  • Humans
  • Isocitrate Dehydrogenase / physiology
  • Metabolism, Inborn Errors / complications*
  • Metabolism, Inborn Errors / metabolism
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Phosphoglycerate Dehydrogenase / physiology

Substances

  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Phosphoglycerate Dehydrogenase