Targeted therapies are under development and show promising activity but are generally not curative since tumors exhibit a remarkable facility for circumventing these agents. There is currently no effective way to treat the disseminated disease. It can only be cured by surgical excision, but the tumor recurs in about 20% of the cases.
Selective multiple quantum coherence lactate skin#
Melanoma is the deadliest skin cancer and the most rapidly increasing malignancy among Caucasian populations throughout the world. Selective Acidification of Melanoma by inhibition of monocarboxylic acid transporters We are extending this approach to other signaling pathways such as ALK and PI3K/AKT inhibitors. We can readily detect this effect by monitoring lactic acid in the tumor (in both mice and men). We have recently demonstrated that administration of specific inhibitors of mTOR produces a marked reduction in glycolytic metabolism as a consequence of decreased expression of hexokinase-2 and other glycolytic enzymes. Detecting tumor response to inhibitors of signal transduction pathways is a major challenge in the clinic. We are also exploring the use of hyperpolarized 13C-labeled substrates to the study of tumors. By monitoring the kinetics of 13C-isotope exchange and fitting these data to a metabolic network model, we can quantitate flux through specific pathways of tumor energy and phospholipid metabolism and translate this into the amount of ATP that is produced from various substrates in tumors. We have recently discovered that NHL tumors in mice are quite unique in that they exhibit extremely well resolved 13C MR spectra. Our focus is largely on non-Hodgkin’s lymphoma (NHL) since this malignancy exhibits roughly a 50% response rate. My laboratory has been developing 31P, 1H and 13C MRS methods as well as physiologically sensitive MRI techniques for monitoring metabolic changes in tumors that predict or detect therapeutic response we generally develop these methods in perfused cells and mice and then translate them to human patients. In 2011 I shared the Gold Medal of the International Society of Magnetic Resonance in Medicine with John Griffiths of Cambridge University for our pioneer work on MRS of cancer. My laboratory initiated the field of NMR spectroscopy of tumors in mice in about 1980 by demonstrating that tumors exhibited detectable changes in bioenergetics, pH and phospholipid metabolism that could be utilized for detection and prediction of therapeutic response. Prediction and Early Detection of Response of non-Hodgkin’s Lymphoma
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