Maria Falck Miniotis1, Thomas R. Eykyn1, Paul Workman2, Martin O. Leach1, Mounia Beloueche-Babari1
1CRUK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 2CRUK Centre for Cancer Therapeutics, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, Surrey, United Kingdom
Deregulated RAS-BRAF-MEK1/2-ERK1/2 signalling is frequently observed in cancer and considerable effort is focused towards developing MEK1/2-targeted therapy. We previously reported that MEK1/2 inhibition causes a reduction in 1H MRS-detectable lactate in human cancer cells. Here we analyse the time-course of the response and investigate the mechanism behind this effect by assessing glucose uptake and lactate dehydrogenase (LDH) activity. We demonstrate that MEK1/2 inhibition leads to decreased lactate production through down-regulation of both glucose uptake and LDH activity. These results show lactate as a potential non-invasive MRS biomarker of response to MEK1/2-targeted therapeutics.