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.