Warburg and Krebs and related effects in cancer

Expert Rev Mol Med. 2019 Sep 27:21:e4. doi: 10.1017/erm.2019.4.

Abstract

Warburg and coworkers' observation of altered glucose metabolism in tumours has been neglected for several decades, which, in part, was because of an initial misinterpretation of the basis of their finding. Following the realisation that genetic alterations are often linked to metabolism, and that the tumour micro-environment imposes different demands on cancer cells, has led to a reinvestigation of cancer metabolism in recent years. Increasing our understanding of the drivers and consequences of the Warburg effect in cancer and beyond will help to identify new therapeutic strategies as well as to identify new prognostic and therapeutic biomarkers. Here we discuss the initial findings of Warburg and coworkers regarding cancer cell glucose metabolism, how these studies came into focus again in recent years following the discovery of metabolic oncogenes, and the therapeutic potential that lies within targeting the altered metabolic phenotype in cancer. In addition, another essential nutrient in cancer metabolism, glutamine, will be discussed.

Keywords: Cancer metabolism; Warburg effect; glucose metabolism; glutamine metabolism; isocitrate dehydrogenase; phosphoglycerate dehydrogenase.

Publication types

  • Review

MeSH terms

  • Animals
  • Glucose / metabolism
  • Glutamine / metabolism
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Phenotype
  • Tumor Microenvironment / genetics

Substances

  • Glutamine
  • Glucose