Thornalley, Paul J. and Rabbani, Naila. (2011) Glyoxalase in tumourigenesis and multidrug resistance. Seminars in Cell and Developmental Biology, Vol.22 (No.3). pp. 318-325. ISSN 1084-9521

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Abstract

Since the discovery by Warburg of high aerobic glycolysis in most tumours in the 1920s, it has remained unclear how to exploit this in chemotherapy. The aim of this review is to assess the evidence for the involvement of the glyoxalase system in tumour growth and multidrug resistance and the importance of the glyoxalase system as a target for anticancer drug development and a source of biomarkers for tumour diagnosis. Increased expression of glyoxalase 1 appears to support the viability of tumour cells with high glycolytic rates. Multidrug resistance conferred by overexpression of glyoxalase 1 suggests mechanisms of toxicity of most current antitumour agents involve, in some part, accumulation of methylglyoxal to cytotoxic levels. The recent finding of glyoxalase 1 gene amplification in tumours and induction of increased glyoxalase 1 expression by malignant transformation and conventional antitumour drug treatment implies a critical role of glyoxalase 1 in innate and acquired multidrug resistance in cancer treatment. Improved understanding of glyoxalase 1 in cancer chemotherapy multidrug resistance is likely vital to achieve improvement of cancer patient survival rates. Advances made to counter glyoxalase 1-linked multidrug resistance with glyoxalase 1 inhibitors and related prodrugs has been translated from in vitro to pre-clinical in vivo studies. Further research is required urgently for next stage clinical translation. Finally, overexpression of glyoxalase 1 may be linked to multidrug resistance in chemotherapy of other disease - such as microbial infections. (C) 2011 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Seminars in Cell and Developmental Biology
Publisher:	Elsevier Science Ltd. / Academic Press Ltd.
ISSN:	1084-9521
Date:	May 2011
Volume:	Vol.22
Number:	No.3
Page Range:	pp. 318-325
Identification Number:	10.1016/j.semcdb.2011.02.006
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Cancer Research UK
URI:	http://wrap.warwick.ac.uk/id/eprint/42089

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