$4.7 Million to Develop Drug Against Epstein-Barr Virus-related Cancers

$4.7 Million to Develop Drug Against Epstein-Barr Virus-related Cancers

The laboratory of Wistar Professor Paul M. Lieberman, Ph.D., has undertaken a historic, groundbreaking project that may change the way doctors treat a variety of human cancers. Historic, because his is the first laboratory in the United States to receive a Seeding Drug Discovery Award from Wellcome Trust, a United Kingdom-based charity. Groundbreaking, because the award will support the development of what may be the first drug to treat Epstein-Barr virus (EBV)-related cancers by attacking the virus as it remains dormant within a patient’s cells.

Paul M. Lieberman, Ph.D.The project is a three-year, multi-stage effort where funding is based on the achievement of defined research milestones, outlined by Lieberman and Troy Messick, Ph.D., a staff scientist in the Lieberman laboratory and co-leader on the project. If successful at each milestone, the laboratory will receive up to $4.7 million in support of their efforts.

The World Health Organization defines EBV as a Class I carcinogen, and it is estimated to cause a small but significant portion of all human cancers. The virus may persist in the human body for decades and cause infected cells to become cancerous. It is estimated that EBV causes nearly 400,000 cases of cancer each year, including Burkitt’s lymphoma, Hodgkin’s lymphoma, non- Hodgkin’s lymphoma, gastric carcinoma and certain oral and throat cancers.

According to Lieberman, EBNA1, a protein produced by EBV, is a prime target for therapeutic intervention. The protein acts as the master switch that regulates viral gene activity and guides the ability of EBV to remain dormant in the body.

“EBNA1 is expressed consistently in all EBV-related cancer and is essential for the virus to reproduce,” said Lieberman. “Knocking out EBNA1, therefore, could likely eliminate latent Epstein-Barr virus and control the growth of EBV-associated cancer.”
To develop an anti-EBV drug, the researchers began a complex screening process to find a small molecule that could chemically bind to EBNA1 and inhibit its ability to function. They began with a library of 600,000 molecular compounds, eventually narrowing the pool down through a series of tests to a handful of leading candidate molecules that have the most potential to serve as the basis of a new anti-EBV drug.

With funds from the Wellcome Trust, the Wistar researchers will further optimize their candidate small molecule inhibitors, with the aim of developing at least one chemical compound into a viable drug candidate. This drug candidate could then be used in clinical trials designed to determine its safety and effectiveness for humans.

“This is an investment in drug discovery, enabling a small team of experts to do the type of translational research typically seen in large drug companies,” said Messick.