Advances in Cancer Research, Volume 127

Professor & Chairman, Dept of Cell & Molecular Pharmacology John C. West Chair of Cancer Research, Medical University of South Carolina, USA

The 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.

Paul B. Fisher, M.Ph., Ph.D., is an accomplished molecular biologist investigating the mechanisms involved in cancer development and progression in order to define improved methods for cancer prevention, detection and therapy. Fisher pioneered a powerful technique to study gene expression in specific tissues or cell types known as subtraction hybridization, which he has used to identify genes involved in many important and medically relevant physiological processes including cancer, neurodegeneration and infectious diseases. Studies in his laboratory focus on understanding the molecular and biochemical reasons for cancer development with a specific focus on understanding how cancers spread, a process called metastasis. The ultimate aim is to use this collected knowledge to bring new, more effective prevention techniques, diagnostic approaches and therapies from the laboratory bench to the patient’s bedside. This is epitomized by his studies involving mda-7/IL-24, a gene that was discovered in his laboratory and has displayed significant clinical efficacy in a phase 1 clinical trial when injected directly into advanced cancers using a form of viral gene therapy. Using a novel cancer terminator virus, Ad.5/3-CTV, that is designed to replicate only within cancer cells while delivering the immune-modulating and toxic mda-7/IL-24 gene, Fisher and his clinical colleagues are developing a clinical trial in patients with glioblastoma multiforme, the most common and deadly form of brain cancer. Fisher has been consistently funded by the National Institutes of Health (NIH) over the past 35 years and is among the top 5 percent of NIH funded investigators during this period. He has published over 500 primary papers and reviews, served on numerous NIH study sections and government and private grant review panels and has over 55 issued patents. He is the recipient of multiple National Cancer Institute (NCI) Program Project Grants; investigator initiated R01 grants from the NIH, NCI and National Institute of General Medical Sciences (NIGMS); private foundation grants from the National Foundation for Cancer Research and the Samuel Waxman Cancer Research Foundation; and an Institutional Research and Academic Career Development Award from the NIH focusing on preparing students from groups underrepresented in the sciences for research careers. Fisher is Professor and Chair of the Department of Human and Molecular Genetics at the Virginia Commonwealth University (VCU) School of Medicine, Founding Director of the VCU Institute of Molecular Medicine and Thelma Newmeyer Corman Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center.