Altered metabolite levels in cancer: implications for tumour biology and cancer therapy

LB Sullivan, DY Gui, MGV Heiden - Nature Reviews Cancer, 2016 - nature.com
LB Sullivan, DY Gui, MGV Heiden
Nature Reviews Cancer, 2016nature.com
Altered cell metabolism is a characteristic feature of many cancers. Aside from well-
described changes in nutrient consumption and waste excretion, altered cancer cell
metabolism also results in changes to intracellular metabolite concentrations. Increased
levels of metabolites that result directly from genetic mutations and cancer-associated
modifications in protein expression can promote cancer initiation and progression. Changes
in the levels of specific metabolites, such as 2-hydroxyglutarate, fumarate, succinate …
Abstract
Altered cell metabolism is a characteristic feature of many cancers. Aside from well-described changes in nutrient consumption and waste excretion, altered cancer cell metabolism also results in changes to intracellular metabolite concentrations. Increased levels of metabolites that result directly from genetic mutations and cancer-associated modifications in protein expression can promote cancer initiation and progression. Changes in the levels of specific metabolites, such as 2-hydroxyglutarate, fumarate, succinate, aspartate and reactive oxygen species, can result in altered cell signalling, enzyme activity and/or metabolic flux. In this Review, we discuss the mechanisms that lead to changes in metabolite concentrations in cancer cells, the consequences of these changes for the cells and how they might be exploited to improve cancer therapy.
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