5th World Congress on Cancer Therapy
University of Pennsylvania, USA
Title: 13C and 1H NMR metabolic markers of therapeutic response upon signal transduction inhibitors in lymphoma cells and in vivo
Biography: Seung-Cheol Lee
The lecture will deal with how NMR methods can be used to detect metabolic changes arising from signaling inhibitor drugs to cancer cells and translational possibilities to be used in the cancer patients. Signaling inhibitor drugs are the major targets of research in the basic science and in the clinic. Early fi nding out whether the targeted drug is working or not to individual patients is a much sought-aft er but not yet met need. Detecting altered metabolism aft er targeted drugs can be a promising strategy to solve it. We are studying metabolism upon signaling inhibitors to mammalian target of rapamycin (mTOR) and bruton tyrosine kinase (BTK) in lymphoma cells and in vivo models. Changes in lactate (glycolysis), glutamate (TCA cycle) and alanine (glutaminolysis) were detectable by 1H and 13C NMR. In a drug resistant cancer cell line, decrease of lactate was accompanied by rebound of glutmate and alanine which suggests metabolic rewiring. On the other hand, in the drug sensitive cell line, all of the above metabolites decreased aft er the signaling inhibition. Time couse 13C NMR data allowed calculating absolute fl uxes in the individual metabolic pathways. We have a 1H MRS lactate imaging technique for cancer patients. Applying the technique to patients being treated with targeted drugs are our ongoing eff orts. Challenges and future directions will also be presented.