In the attempt of developing innovative anticancer treatments, growing interest has recently focused on the peculiar metabolic properties of cancer cells. In this context, lactate dehydrogenase (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 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 are in support of 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 to evaluate in the near future the real potential of LDH inhibition in anticancer treatment, also making possible the identification of the most responsive neoplastic conditions.

Inhibition of lactate dehydrogenase activity as an approach to cancer therapy

FIUME, LUIGI;MANERBA, MARCELLA;VETTRAINO, MARINA ELEONORA;DI STEFANO, GIUSEPPINA
2014

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, lactate dehydrogenase (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 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 are in support of 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 to evaluate in the near future the real potential of LDH inhibition in anticancer treatment, also making possible the identification of the most responsive neoplastic conditions.
Luigi FIUME; Marcella MANERBA; Marina VETTRAINO; Giuseppina DI STEFANO
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/260088
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