April’s SLAS Discovery now available
Oak Brook, IL – April’s edition of SLAS Discovery features the cover article, “Maximizing the Value of Cancer Drug Screening in Multicellular Tumor Spheroid Cultures: A Case Study in Five Head and Neck Squamous Cell Carcinoma Cell Lines.” Stanton J. Kochanek, Ph.D., David A. Close, Ph.D., Daniel P. Camarco, Ph.D., and Paul A. Johnston, Ph.D., (University of Pittsburgh, PA, USA) disseminate their recent study that shows how incorporating morphology and dead cell readouts into cancer drug screening helps improve the drug selection rate.
Consistent with solid tumors, multicellular tumor spheroids (MCTS) develop gradients of nutrient distribution and oxygen concentration resulting in diverse microenvironments with differential proliferation and drug distribution zones. Kochanek, Close, Camarco and Johnston produced head and neck squamous cell carcinoma (HNSCC) MCTSs and used viability reagents and imaging methods to measure the effects of anti-cancer drug exposure. This step revealed that cell viability reagents under-estimate the impact of drug exposure in HNSCC MCTS cultures, but that incorporating morphology and dead cell readouts increased the number of drugs judged to have substantially impacted MCTS cultures.
A multi-parameter drug impact score provided a way to stratify MCTS drug responses and maximize the value of these more physiologically relevant tumor cultures.
Currently, cancer drug approval rates are less than 5%, while the overall probability of success in oncology clinical trials is 3.4%. Kochanek, Close, Camarco and Johnston continue to build on their current research to help improve these cancer drug discovery and development success rates through the use of more physiologically relevant and complex 3D models featured in this study.
The group’s lead researcher, Paul A. Johnston, has 30 years of drug discovery experience in the pharmaceutical, biotechnology and academic sectors. As an innovator of cell-based lead generation, he pioneered the implementation of high-content imaging technology for drug discovery, and in 2005 helped create the University of Pittsburgh Molecular Library Screening Center (Pittsburgh, PA, USA). In 2011, Johnston established his own chemical biology laboratories within the University’s Department of Pharmaceutical Sciences of the School of Pharmacy in order to conduct research on the application of novel drug discovery strategies to find new and effective drugs or drug combinations for prostate cancer, melanoma, head and neck cancer and hepatocellular carcinoma.