@article{a4d8840fcfb24bb8ba7fe72ffff7a9f6,
title = "Disruption of glycogen utilization markedly improves the efficacy of carboplatin against preclinical models of clear cell ovarian carcinoma",
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.",
keywords = "2DG, Clear cell ovarian cancer, Glycogen",
author = "Tashbib Khan and Yaowu He and Thomas Kryza and Harrington, {Brittney S.} and Gunter, {Jennifer H.} and Sullivan, {Mitchell A.} and Tahleesa Cuda and Rebecca Rogers and Davies, {Claire M.} and Amy Broomfield and Madeline Gough and Wu, {Andy C.} and Thomas McGann and Weroha, {S. John} and Paul Haluska and Forbes, {Josephine M.} and Armes, {Jane E.} and Barry, {Sinead C.} and Coward, {Jermaine I.} and Nisha Jagasia and Naven Chetty and Snell, {Cameron E.} and Rohan Lourie and Perrin, {Lewis C.} and Hooper, {John D.}",
note = "Funding Information: Funding: This study was supported by a grant from the Australia New Zealand Gynaecological Oncology Group and philanthropic support from the Mater Foundation (JDH) and a higher degree scholarship awarded by The University of Queensland Graduate School (Tashbib Khan). MAS is supported by a Mater Foundation McGuckin Early Career Fellowship and the University of Queensland Amplify Initiative. We acknowledge the Translational Research Institute for providing the core facilities that enabled this research, particularly the Biological Resources Facility, Microscopy Facility and Preclinical Imaging Facility. The Translational Research Institute is support financially by the Australia Federal Government. Funding Information: This study was supported by a grant from the Australia New Zealand Gynaecological Oncology Group and philanthropic support from the Mater Foundation (JDH) and a higher degree scholarship awarded by The University of Queensland Graduate School (Tashbib Khan). MAS is supported by a Mater Foundation McGuckin Early Career Fellowship and the University of Queensland Amplify Initiative. We acknowledge the Translational Research Institute for providing the core facilities that enabled this research, particularly the Biological Resources Facility, Microscopy Facility and Preclinical Imaging Facility. The Translational Research Institute is support financially by the Australia Federal Government. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = apr,
doi = "10.3390/cancers12040869",
language = "English (US)",
volume = "12",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",
}