Maria Falck Miniotis1, Paul Workman2, Martin O. Leach1, Mounia Beloueche-Babari1
1Cancer Research UK Clinical Magnetic Resonance Research Group, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, Surrey, UK; 2Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research & The Royal Marsden Hospital, Sutton, Surrey, UK
RAS-B-RAF-MEK-ERK signalling is often deregulated in cancer and represents a significant target for mechanism-based drugs. Our aim was to investigate whether inhibition of this signalling pathway in human cancer cells could lead to magnetic resonance spectroscopy detectable changes in glycolysis that may serve as biomarkers of target suppression. Our findings demonstrate that MEK1/2 signalling inhibition with CI-1040 or PD325901 leads to decreased intracellular lactate levels in human melanoma, colorectal and breast carcinoma cell lines. These results suggest lactate as a potential non-invasive MRS biomarker of response to MEK1/2 targeted therapeutics in human cancer cells.
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