Sosnovsky Lecturers
Thursday, April 26, 2012, 3:00pm
Peng Huang, University of Texas MD Anderson Cancer Center
Metabolic Alterations in Cancer: Mechanisms and Therapeutic Implications
Cancer metabolism is an important area of research.This lecture will focus on two major metabolic changes frequently observed in cancer cells: increased aerobic glycolysis (the Warburg effect) and oxidative stress. The potential mechanisms that contribute to these metabolic alterations, including oncogenic signals, mitochondrial dysfunction, and tumor tissue microenvironment will be discussed. The role of such metabolic alterations in affecting cancer cell viability and drug sensitivity will also be explored in the context of developing new therapeutic strategies to effectively and preferentially kill cancer cells.Special emphasis will focus on mitochondrial dysfunction as a key event that links malignant transformation to metabolic alterations, and the relevant biochemical basis for developing novel therapeutic strategies.
Location: Chemistry 180
Host: Prof. Sosnovsky
Friday, April 27, 2012, 3:00pm
Peng Huang, University of Texas MD Anderson Cancer Center
Novel Strategies to Target Metabolic Alterations in Cancer with Improved Therapeutic Selectivity
Increased glycolysis and oxidative stress are two prominent metabolic alterations in cancer cells.These biochemical changes may provide an important basis for developing new therapeutic strategies to selectively kill cancer cells. It is hypothesized that since cancer cells with mitochondrial dysfunction and compromised ability to produce ATP through oxidative phosphorylation may be more dependent on glycolysis for generation of ATP and metabolic intermediates for cell survival and proliferation, inhibition of this metabolic pathway by targeting the key glycolytic enzymes may preferentially impact cancer cells.Similarly, due to the active generation of reactive oxygen species (ROS), cancer cells are more dependent on antioxidants such as glutathione to counteract oxidative stress, rendering them highly vulnerable to redox-modulating agents.This seminar will focus on two metabolic intervention strategies for potential cancer treatment: (1) the use of glycolytic inhibitors such as 3-bromopyruvate and its analogs to block energy production in cancer cells, aiming at preferential killing of malignant cells with mitochondrial dysfunction, and (2) the use of redox-modulating agents such as PEITC to selectively target cancer cells with elevated ROS stress.Experimental evidence will be presented to illustrate the mechanisms of action of these two classes of compounds and their potential combination with conventional anticancer agents to improve therapeutic activity and overcome drug resistance.
Location: Chemistry 180
Host: Prof. Sosnovsky