Cancer heterogeneity is not compatible with one unique cancer cell metabolic map

Abstract

The Warburg effect and its accompanying metabolic features (anaplerosis, cataplerosis) are presented in textbooks and reviews as a hallmark (general characteristic): the metabolic map of cancer. On the other hand, research articles on specific tumors since a few years emphasize various biological features of different cancers, different cells in a cancer and the dynamic heterogeneity of these cells. We have analysed the research literature of the subject and show the generality of a dynamic, evolving biological and metabolic, spatial and temporal heterogeneity of individual cancers. We conclude that there is no one metabolic map of cancer but several and describe the two extremes of a panel from the hypoxic to the normoxic state. The implications for the significance of general 'omic' studies, and on therapeutic conclusions drawn from them and for the diagnostic use of fractional biopsies is discussed.