Letter to the Editor
Comment on: Targeting homologous recombinationmediated DNA repair in cancer Luigi Fiume University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Italy
Expert Opin. Ther. Targets Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
Expert Opin. Ther. Targets (2014) 18(7):833
In the April issue of ‘Expert Opinion on Therapeutic Targets’, Carvalho and Kanaar reviewed researches aimed at increasing the anticancer activity of genotoxic drugs by association with small molecules able to hinder DNA repair [1]. As stressed by Li [2], a caveat of this interesting approach is the potential for secondary malignancies that might emerge after successful control of the primary cancer. An anticancer strategy presently pursued rests on the inhibition of lactate dehydrogenase (LDH), which results in block of aerobic glycolysis and consequently in reduction in ATP levels selectively in neoplastic cells [3]. Since DNA damage repair requires a chromatin remodeling that needs substantial amounts of ATP [4], the impairment of aerobic glycolysis could hinder the DNA repair in neoplastic cells and spare normal cells. Accordingly, it could be worthwhile to verify whether the recently obtained inhibitors of LDH, which inhibit aerobic glycolysis in neoplastic cultured cells by selectively blocking the enzyme [5], enhance the DNA damaging effects of the genotoxic drugs.
Declaration of interest The author states no conflict of interest and has received no payment in preparation of this manuscript. Bibliography 1.
Carvalho JFS, Kanaar R. Targeting homologous recombination-mediated DNA repair in cancer. Expert Opin Ther Targets 2014;18:427-58
2.
Li CY. Inhibitors of DNA repair for cancer therapy, ready for prime time? Transl Cancer Res 2012;1:4-5
3.
Fiume L, Manerba M, Vettraino M, et al. Inhibition of lactate
dehydrogenase activity as an approach to cancer therapy. Future Med Chem 2014;6:429-45 4.
5.
Lans H, Marteijn JA, Vermeulen W. ATPdependent chromatin remodeling in the DNA-damage response. Epigenetics Chromatin 2012;5:4 Billiard J, Dennison JB, Briand J, et al. Quinoline 3-sulfonamides inhibit
10.1517/14728222.2014.925617 © 2014 Informa UK, Ltd. ISSN 1472-8222, e-ISSN 1744-7631 All rights reserved: reproduction in whole or in part not permitted
lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab 2013;1:19
Affiliation Luigi Fiume University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Italy E-mail: [email protected]
833
Comment on: Targeting homologous recombinationmediated DNA repair in cancer Luigi Fiume University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Italy
Expert Opin. Ther. Targets Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
Expert Opin. Ther. Targets (2014) 18(7):833
In the April issue of ‘Expert Opinion on Therapeutic Targets’, Carvalho and Kanaar reviewed researches aimed at increasing the anticancer activity of genotoxic drugs by association with small molecules able to hinder DNA repair [1]. As stressed by Li [2], a caveat of this interesting approach is the potential for secondary malignancies that might emerge after successful control of the primary cancer. An anticancer strategy presently pursued rests on the inhibition of lactate dehydrogenase (LDH), which results in block of aerobic glycolysis and consequently in reduction in ATP levels selectively in neoplastic cells [3]. Since DNA damage repair requires a chromatin remodeling that needs substantial amounts of ATP [4], the impairment of aerobic glycolysis could hinder the DNA repair in neoplastic cells and spare normal cells. Accordingly, it could be worthwhile to verify whether the recently obtained inhibitors of LDH, which inhibit aerobic glycolysis in neoplastic cultured cells by selectively blocking the enzyme [5], enhance the DNA damaging effects of the genotoxic drugs.
Declaration of interest The author states no conflict of interest and has received no payment in preparation of this manuscript. Bibliography 1.
Carvalho JFS, Kanaar R. Targeting homologous recombination-mediated DNA repair in cancer. Expert Opin Ther Targets 2014;18:427-58
2.
Li CY. Inhibitors of DNA repair for cancer therapy, ready for prime time? Transl Cancer Res 2012;1:4-5
3.
Fiume L, Manerba M, Vettraino M, et al. Inhibition of lactate
dehydrogenase activity as an approach to cancer therapy. Future Med Chem 2014;6:429-45 4.
5.
Lans H, Marteijn JA, Vermeulen W. ATPdependent chromatin remodeling in the DNA-damage response. Epigenetics Chromatin 2012;5:4 Billiard J, Dennison JB, Briand J, et al. Quinoline 3-sulfonamides inhibit
10.1517/14728222.2014.925617 © 2014 Informa UK, Ltd. ISSN 1472-8222, e-ISSN 1744-7631 All rights reserved: reproduction in whole or in part not permitted
lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab 2013;1:19
Affiliation Luigi Fiume University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Italy E-mail: [email protected]
833
