January 15, 2015
By Mark Terry, BioSpace.com Breaking News Staff
In early December, three researchers at the Perelman School of Medicine at the University of Pennsylvania and The Wistar Institute were awarded a Discovery Fast Track Challenge grant from GlaxoSmithKline . Yesterday it was announced that the team of scientists are now working with GSK Discovery Partnerships with Academia to expand and refine their work.
Donna George and Julia Leu are with the Department of Genetics at the University of Pennsylvania. Maureen Murphy is affiliated with The Wistar Institute. “The goal of our work is to identify compounds that can be developed as effective therapeutics for a variety of cancers,” said George in a statement. “We are very pleased to have been selected for this award. The new partnership with GSK provides us with access to valuable resources and scientific expertise to help move our basic research ideas into practical treatments.”
For the Challenge, GSK selected 14 research project proposals from 428 entries from 26 countries. The Penn/Winstar team focuses on developing a drug that target Heat Shock Protein 70 (HSP70), which is a stress-induced protein found in low levels in normal cells, but is common in tumor cells. The protein has been tied to autophagy, which is a biological process involving self-digestion, a strategy the body uses to survive stressful situations. Cancer cells also use autophagy.
“Normal cells don’t need HSP70 to survive, but cancer cells do,” said Murphy in a statement. “It’s the Achilles heel of cancer. If you limit autophagy, normal cells will live for a time. Cancer cells will die immediately.”
The three scientists identified several HSP70 inhibitors that have demonstrated effectiveness against lymphoma and melanoma in mice. The team was studying the tumor suppressor protein p53 and observed that a molecule called 2-Phenylethynesulfonamide (PES) changed the p53 protein activity. Eventually their research led to the discovery of HSP70.
As part of the challenge, the scientists are utilizing GSK’s enormously compound library and drug screening facility to hunt for drugs that target HSP70. Murphy notes that without GSK’s resources, they were limited to performing a small number of assays in their laboratory, but GSK has the capabilities of screening tens of thousands of compounds in a high-throughput environment.
“We are looking for new drugs that target HSP70, and modifying our existing drug candidates to make them better,” said Murphy in a statement. “When you look at their drug screening facility, it is unbelievable. It’s the size of a football field.”
