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.
Keywords