Description
Title: Investigation of central nervous system tumor metabolism in patients undergoing surgical resection PI- Kumar Pichumani, PhD coPI- David Baskin, MD Interest in the clinical potential of tumor intermediary metabolism dates to the 1920, when Otto Warburg had demonstrated that aggressive tumors had an inclination towards conversion of glucose into lactate, and proposed that the metabolic idiosyncrasies of tumors could be exploited to treat cancer. Warburg effect further states that transformed cells were uniformly dependent on glycolysis due to impaired or limited mitochondrial metabolism. However, it fails to explain growth of tumors requirement of increased demand for energy and macromolecular synthesis (proteins, lipids, nucleic acids) which are generated from the citric acid cycle intermediates in mitochondria. Therefore, there is a fundamental paradox between limited mitochondrial activity and the metabolic demands of tumor growth. Recently, I along with a team of clinicians at University of Texas Southwestern Medical Center, Dallas, TX have demonstrated that brain tumors have the capacity to fully oxidize glucose and acetate in the mitochondria in addition to excess production of lactate (Warburg effect). I and Dr. Baskin, plan to continue to further explore the metabolic complexities/phenotype of various histologically distinct brain tumors (Glioblastoma, Meningioma, Metastasis Brain tumors and Pituitary tumors). We will use sterile, pyrogen free, non-radioactive stable carbon isotope (13C) enriched nutrients such as glucose and acetate on patients who are scheduled to undergo surgical removal of the tumor mass. Fraction of the tumor tissue will be used for 13C-NMR (Magnetic Resonance Spectroscopy) analysis and mathematical modeling extract all the in-vivo tumor metabolic information. It is anticipated that the proposed study will provide a comprehensive view of the substrate utilization of human cancer patients in vivo and also key metabolic vulnerabilities will likely be uncovered that may be further exploited for therapeutic targeting.
