Wistar-Led Team Awarded More Than $12 Million Grant from the NCI to Investigate Link Between Epstein-Barr Virus and Carcinomas

PHILADELPHIA, PA, July 26, 2023 (GLOBE NEWSWIRE) — It’s been known since the 1960s that Epstein-Barr Virus (EBV) causes a variety of cancers, but research has overwhelmingly focused on its connection to lymphomas. Now, a multidisciplinary team of scientists led by The Wistar Institute has been awarded a more than $12 million National Cancer Institute (NCI) Program Project Grant (P01), a highly competitive five-year grant that includes a crosssection of researchers from various disciplines and institutions throughout the country. The multidisciplinary team led by Wistar scientists is exploring the role of Epstein-Barr Virus in epithelial cancers. Epithethelial cells form functional structures in organ tissue throughout the human body; they are often the site for solid organ cancers, including the most common cancers, which are known as carcinomas.

The new research will focus on basic questions about how EBV infection of normal epithelial cells transforms them into cancer-cells. Scientists also intend to build on this research to identify better and more selective therapeutic targets.
“We are investigating unexplored aspects of EBV and malignancies, potentially uncovering unique characteristics or pathways that can be targeted for therapeutic intervention,” said Italo Tempera, Ph.D., associate professor of the Gene Expression & Regulation Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute. “This fresh perspective could lead to groundbreaking discoveries and innovative treatment strategies for EBV and epithelial malignancies.”

The project brings together scientists from The Wistar Institute and Harvard University, including experts in epigenetics, metabolomics and drug discovery. It’s the first time researchers from this variety of disciplines have combined their efforts to focus entirely on the EBV-epithelial cancer link.

“We’ve put together a new strategy, a new way of attacking the problem,” said Paul Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor and director of the Center for Chemical Biology and Translational Medicine at Wistar. “By working together across different modalities, there’s an opportunity for each of us to learn from the synergy and expertise of the other investigators.”

EBV is one of the most common human viruses, infecting an estimated 95% of people by the time they reach adulthood. Symptoms are usually mild, and most people recover within a few weeks. However, the virus can remain latent in the human body for years or even decades, and it causes some people to develop cancer later in life. 

While research has historically focused on lymphomas, EBV-linked epithelial cancers are both more common and more deadly. Epithelial cancers represent 75% of the 200,000 EBV-related cancer cases diagnosed each year, and these cancers also have higher mortality rates and treatment failures. 

“This grant put together a team that is now focused on this type of cancer that has been neglected, even though it’s the most common form of EBV cancers,” Lieberman said. The grant will fund three main research projects. The first will look at how EBV establishes a long-term infection within epithelial cells. The second will study how it causes genetic and metabolic changes to trigger cancer growth. Finally, researchers will use these findings to investigate new therapeutic strategies. 

The research builds on past work by Lieberman’s lab, which has focused on developing small molecule inhibitors targeting EBV. He said the new project would focus on studying drugs that are already in development, and looking for ways to make them more targeted or use them in combination with other therapies. 

Tempera said the group’s integrated approach sets it apart.“Our project will study both metabolic and epigenetic vulnerabilities simultaneously,” he said. “Combining these two aspects can provide a comprehensive understanding of the role of EBV infection in cancer and its underlying mechanisms, leading to unique insights and therapeutic opportunities.” 

Co-authors: Ben Gewurz of Harvard; Joseph Salvino, Samantha Soldan, Andrew Kossenkov, Louise Showe, and Qin Liu of Wistar.

Darien Sutton
The Wistar Institute

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