13C and 1H NMR metabolic markers of therapeutic response upon signal transduction inhibitors in lymphoma cells and in vivo

5^th World Congress on Cancer Therapy

September 28-30, 2015 Atlanta, USA

Seung-Cheol Lee

University of Pennsylvania, USA

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

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 finding out whether the targeted drug is working or not to individual patients is a much sought-after but not yet met need. Detecting altered metabolism after 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 after the signaling inhibition. Time couse 13C NMR data allowed calculating absolute fluxes 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 efforts. Challenges and future directions will also be presented.

Biography :

Lee has completed his PhD from KAIST, Korea and postdoctoral studies from the Korea Basic Science Insititute and the University of Pennsylvania. He is currently a research assistant professor of radiology at the University of Pennsylvania. His research areas are 1H, 31P and 13C NMR of cancer cells, xenograft models and patients for prediction and detection of therapeutic response. He has published ~20 papers in the peer reviewed journals.

Email: seungch@mail.med.upenn.edu