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BioMed Research International
Volume 2013 (2013), Article ID 946206, 12 pages
http://dx.doi.org/10.1155/2013/946206
Review Article

Emerging Metabolic Targets in the Therapy of Hematological Malignancies

University of Bern, Department of Clinical Research, Division of Pediatric Hematology/Oncology, Murtenstrasse 31, 3010 Bern, Switzerland

Received 24 April 2013; Revised 15 July 2013; Accepted 15 July 2013

Academic Editor: Beric Henderson

Copyright © 2013 Zaira Leni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

During the last decade, the development of anticancer therapies has focused on targeting neoplastic-related metabolism. Cancer cells display a variety of changes in their metabolism, which enable them to satisfy the high bioenergetic and biosynthetic demands for rapid cell division. One of the crucial alterations is referred to as the “Warburg effect”, which involves a metabolic shift from oxidative phosphorylation towards the less efficient glycolysis, independent of the presence of oxygen. Although there are many examples of solid tumors having altered metabolism with high rates of glucose uptake and glycolysis, it was only recently reported that this phenomenon occurs in hematological malignancies. This review presents evidence that targeting the glycolytic pathway at different levels in hematological malignancies can inhibit cancer cell proliferation by restoring normal metabolic conditions. However, to achieve cancer regression, high concentrations of glycolytic inhibitors are used due to limited solubility and biodistribution, which may result in toxicity. Besides using these inhibitors as monotherapies, combinatorial approaches using standard chemotherapeutic agents could display enhanced efficacy at eradicating malignant cells. The identification of the metabolic enzymes critical for hematological cancer cell proliferation and survival appears to be an interesting new approach for the targeted therapy of hematological malignancies.