4.5 Article

An update on therapeutic opportunities offered by cancer glycolytic metabolism

Journal

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 24, Issue 21, Pages 4915-4925

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2014.09.041

Keywords

Cancer metabolism; Warburg effect; Glycolysis; Hypoxia; Antitumor agents

Funding

  1. IEO - Italy
  2. NIH - United States [R01M098453]

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Almost all invasive cancers, regardless of tissue origin, are characterized by specific modifications of their cellular energy metabolism. In fact, a strong predominance of aerobic glycolysis over oxidative phosphorylation (Warburg effect) is usually associated with aggressive tumour phenotypes. This metabolic shift offers a survival advantage to cancer cells, since they may continue to produce energy and anabolites even when they are exposed to either transient or permanent hypoxic conditions. Moreover, it ensures a high production rate of glycolysis intermediates, useful as building blocks for fast cell proliferation of cancer cells. This peculiar metabolic profile may constitute an ideal target for therapeutic interventions that selectively hit cancer cells with minimal residual systemic toxicity. In this review we provide an update about some of the most recent advances in the discovery of new bioactive molecules that are able to interfere with cancer glycolysis. (C) 2014 The Authors. Published by Elsevier Ltd.

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