Redox and Cancer Part A

Professor & Chairman, Dept of Cell & Molecular Pharmacology John C. West Chair of Cancer Research, Medical University of South Carolina, USAThe Tew laboratory maintains an interest in using redox pathways as a platform to develop therapeutic strategies through drug discovery/development and biomarker identification. We interrogate how reactive oxygen and nitrogen species (ROS/RNS) impact cancer cells and develop novel drugs that impact on glutathione based pathways. Our research efforts have been integral to studies that have identified glutathione S-transferases (GST) as important in drug resistance, catalytic detoxification and as arbiters of kinase-mediated cell signaling events. In addition, we have been instrumental in defining how GSTP contributes to the process by which cells respond to ROS by selective addition of glutathione to specific protein clusters, so called S-glutathionylation. Each of these research areas has had broad impact on a number of cancer disciplines. Moreover, we have also been seminally involved in the Phase I to III clinical testing of three oncology drugs, Telcyta, Telintra and NOV-002. Other ongoing translational efforts have produced two ongoing clinical trials to measure the effectiveness of serum S-glutathionylated serine proteinase inhibitors as possible biomarkers for exposure to hydrogen peroxide mouthwashes and radiation.

• 1. Reactive Oxygen Species in Normal and Tumor Stem Cells2. Emerging Regulatory Paradigms in Glutathione Metabolism3. Gamma-Glutamyl Transpeptidase: Redox Regulation and Drug Resistance4. Pleiotropic Functions of Glutathione S-Transferase P5. A Comparison of Reversible versus Irreversible Protein Glutathionylation6. Glutathione Transferases in the Bioactivation of Azathioprine7. Thioredoxin and Hematological Malignancies8. Role of the Keap1-Nrf2 Pathway in Cancer

Praise for the Series:"Excellent, highly informative, in-depth reviews... expertly written, up-to-date, and well-referenced." --JOURNAL OF MEDICINAL CHEMISTRY