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British Journal of Cancer (2008) 99, 989 994 & 2008 Cancer Research UK All rights reserved 0007 0920/08 $32.00
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Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer
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A PARADIGM SHIFT IS NEEDED IN CANCER THERAPEUTICS Although some battles have been won since the declaration of the war on cancer in 1971 in the United States, the war is ongoing. Despite enormous investments from industry and the public, oncology has an impressively poor success rate in the clinical development of effective investigational drugs; less than a third of that in cardiovascular or infectious diseases (Kamb et al, 2007). Drug development in oncology has typically focused on targets essential for the survival of all dividing cells, leading to narrow therapeutic windows. Non-essential targets offer more selectivity but little efficacy. It is extremely rare to find an essential target that is unique to cancer cells; the dependence of CML cells on Ableson kinase is only induced by a chromosomal translocation in the malignant clone, making the efficacy and selectivity of imatinib for CML an exception in cancer therapy (Kamb et al, 2007). The most important reason for the poor performance of cancer drugs is the remarkable heterogeneity and adaptability of cancer cells. The molecular characteristics of histologically identical cancers are often dissimilar and molecular heterogeneity frequently exists within a single tumour. The view that there are many different types of cancers is increasingly shared by scientists and clinical oncologists. This has important implications, including the realisation that specific drugs have to be developed and tested for molecularly defined tumours and effects in one might not necessarily be relevant to another cancer.
ED Michelakis*,1, L Webster1 and JR Mackey2
1Department of Medicine, University of Alberta, Edmonton, Canada; 2Department of Oncology, University of Alberta, Edmonton, Canada
The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a...