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Published VersionCC BY V4.0, Open Access
Journal article
Disruption of Glycogen Utilization Markedly Improves the Efficacy of Carboplatin against Preclinical Models of Clear Cell Ovarian Carcinoma
Cancers, Vol.12(4), pp.1-17
2020
PMID: 32260077
Abstract
High stage and recurrent ovarian clear cell carcinoma (OCC) are associated with poor prognosis and resistance to chemotherapy. A distinguishing histological feature of OCC is abundant cytoplasmic stores of glucose, in the form of glycogen, that can be mobilized for cellular metabolism. Here, we report the effect on preclinical models of OCC of disrupting glycogen utilization using the glucose analogue 2-deoxy-D-glucose (2DG). At concentrations significantly lower than previously reported for other cancers, 2DG markedly improves the efficacy in vitro of carboplatin chemotherapy against chemo-sensitive TOV21G and chemo-resistant OVTOKO OCC cell lines, and this is accompanied by the depletion of glycogen. Of note, 2DG doses-of more than 10-fold lower than previously reported for other cancers-significantly improve the efficacy of carboplatin against cell line and patient-derived xenograft models in mice that mimic the chemo-responsiveness of OCC. These findings are encouraging, in that 2DG doses, which are substantially lower than previously reported to cause adverse events in cancer patients, can safely and significantly improve the efficacy of carboplatin against OCC. Our results thus justify clinical trials to evaluate whether low dose 2DG improves the efficacy of carboplatin in OCC patients.
Details
- Title
- Disruption of Glycogen Utilization Markedly Improves the Efficacy of Carboplatin against Preclinical Models of Clear Cell Ovarian Carcinoma
- Authors
- Tashbib Khan - Translational Research InstituteYaowu he - The University of QueenslandThomas Kryza - The University of QueenslandBrittney S Harrington - The University of QueenslandJennifer H Gunter - Queensland University of TechnologyMitchell A Sullivan - The University of QueenslandTahleesa Cuda - The University of QueenslandRebecca Rogers - The University of QueenslandClaire M Davies - The University of QueenslandAmy Broomfield - Mater Health ServicesMadeline Gough - Mater Health ServicesAndy C K Wu - The University of QueenslandThomas McGann - The University of QueenslandS John Weroha - Mayo ClinicPaul Haluska - Mayo ClinicJosephine M Forbes - The University of QueenslandJane E Armes - The University of QueenslandSinead C Barry - The University of QueenslandJermaine I Coward - The University of QueenslandNisha Jagasia - Mater Health ServicesNaven Chetty - Mater Health ServicesCameron E Snell - The University of QueenslandRohan Lourie - The University of QueenslandLewis C Perrin - The University of QueenslandJohn D Hooper (Corresponding Author) - Translational Research Institute
- Publication details
- Cancers, Vol.12(4), pp.1-17
- Publisher
- MDPI AG
- Date published
- 2020
- DOI
- 10.3390/cancers12040869
- ISSN
- 2072-6694
- PMID
- 32260077
- Copyright note
- © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991035095602621
- Output Type
- Journal article
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