title: Inhibition of lactate dehydrogenase activity as an approach to cancer therapy.
abstract: In the attempt of developing innovative anticancer treatments, growing interest has recently focused on the peculiar metabolic properties of cancer cells. In this context, LDH, which converts pyruvate to lactate at the end of glycolysis, is emerging as one of the most interesting molecular targets for the development of new inhibitors. In fact, because LDH activity is not needed for pyruvate metabolism through the TCA cycle, inhibitors of this enzyme should spare glucose metabolism of normal non-proliferating cells, which usually completely degrade the glucose molecule to CO2. This review is aimed at summarizing the available data on LDH biology in normal and neoplastic cells, which support the anticancer therapeutic approach based on LDH inhibition. These data encouraged pharmaceutical industries and academic institutions in the search of small-molecule inhibitors and promising candidates have recently been identified. The availability of inhibitors with drug-like properties will allow the evaluation in the near future of the real potential of LDH inhibition in anticancer treatment, also making the identification of the most responsive neoplastic conditions possible.
authors.affiliation: Department of Experimental, Diagnostic & Specialty Medicine, University of Bologna, via San Giacomo, 14-40126 Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fiume
authors.forename: Marcella
authors.initials: M
authors.lastname: Manerba
authors.forename: Marina
authors.initials: M
authors.lastname: Vettraino
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D020836:Protein Structure, Quaternary; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D054852:Small Molecule Libraries; D007770:L-Lactate Dehydrogenase