Yuen-Li Chung1, Helen Troy1, Ian R. Judson2, John R. Griffiths3, Martin O. Leach1, Thomas R. Eykyn1
1CR-UK and ESPRC Cancer Imaging Centre, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2CR-UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 3Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom
Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor and is found to be an anti-cancer agent. The aim of this work was to study the mechanism of action of DCA and to develop a non-invasive biomarker for response following PDK inhibition. DCA treatment caused G1 arrest and a dramatic drop in the conversion of hyerpolarised 13C-labelled pyruvate to lactate. 1H-MRS of the culture media of DCA-treated cells also showed a reduction in steady state eupolarised lactate production and increased alanine uptake. These changes have potential as non-invasive biomarkers of drug action. DCA treatment also altered phospholipid metabolism, which could provide further biomarkers of response.