(596ba) Lead Identification, Optimization, and Characterization of Novel Cancer Treatment Strategies Using Repositioned Drugs

Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance.  Of these deaths prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women.  Developing new drugs for the treatment of cancer is both a slow and expensive process.  It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market.  However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA).  The research presented describes the testing and identification of novel methods for treating many human carcinomas using drugs previously approved by the FDA.  Approved drugs that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells will be identified in well plate based experiments and leads that are identified will be optimized using high-throughput microfluidic devices.  Identification of FDA approved drugs that demonstrate the ability to depolarize the mitochondria of cancer cells will also be carried out coupled with the testing of these drugs in potential delivery vehicles.  Mechanistic evaulations of lead candidates are also presented.