October 11, 2021

The Spirit of Innovation: Leading the way in cancer virology

Some viruses are mild and cause little to no harm to humans. Others like SARS-CoV-2 – the virus that causes the disease known as COVID-19 – are significantly more dangerous. And bad viruses don’t just cause pandemics. They can also cause cancer.

It’s estimated that roughly 15-20 percent of cancers are associated, in some way, with a virus. Whether it’s Human Papillomavirus (HPV), Human Immunodeficiency Virus (HIV) or Hepatitis C – just to name a few – viruses and cancer frequently go hand-in-hand.

Fortunately, virology researchers at the University of Wisconsin have been studying the virus/cancer relationship for decades, and the work is still going strong. Today, nearly half the virology researchers on campus are dedicated to unraveling the mysteries of tumor virology in its many different forms.

And that’s where the Human Cancer Virology program at the UW Carbone Cancer Center comes in. Led by Shannon Kenney, MD, and Robert Kalejta, PhD, the program is comprised of over a dozen virologists studying the seven established human tumor viruses.

“Our main goals are doing basic science research to understand how these viruses replicate, how they cause tumors, and to identify potential areas that we could target with treatments,” Kalejta said. “Increasingly, we are working on translating those to discoveries to the clinic, so we’re actually developing drugs or therapies based on not only our research but other research as well.”

When the National Cancer Act of 1971 was signed into law, the connection between viruses and cancer was not widely studied. It wasn’t until virologist and geneticist Howard Temin, PhD, made history at UW with his discovery of reverse transcriptase – that is, an enzyme that copies RNA into DNA and how viruses used this to produce cancer cells – that the field really took off.

That discovery bucked the conventional wisdom in molecular biology at the time, and for his work, Temin was awarded the Novel Prize in 1975. Temin was also key in securing a tumor virology Program Project grant from the National Cancer Institute, funding that has now been continuously renewed for 45 years, allowing virology research to thrive at UW while fostering a national reputation for innovation in the field.

“Basically since the inception of cancer biology, we’ve been leading the way in cancer virology,” Kalejta said.

While the virologists of UW Carbone and the McArdle Laboratory for Cancer Research are studying all the known viruses associated with cancer, they’ve developed over the years a great deal of expertise and knowledge specifically with Human Papillomavirus (HPV) and Epstein-Barr Virus (EBV). And it’s the research being done on EBV that really demonstrates the comprehensive way this work is approached at UW.

You might not be as familiar with EBV, but there’s a good chance it’s already in your system. Most of us will pick it up at some point during our lives, usually during childhood where it goes fairly unnoticed, but sometimes during the teenage years, leading to cold-like symptoms or the development of mononucleosis: also known as the “kissing disease.”

Once the virus runs its course, it remains in the body in an inactive or dormant form. But for some individuals – especially those with weakened immune systems – the virus can reactivate later in life. And that can increase the risk of developing certain cancers in epithelial tissue, including gastric and throat cancers.

Scientists like Bill Sugden, PhD, have played a very important role in figuring out how the virus replicates during latent infection. In Kenney’s lab, scientists have been working to create new mouse models to help understand how EBV causes cancer. And additional teams are working to develop specific treatments for EBV-associated tumors.

“I think we probably have more EBV people in one department than any other department in the world,” Kenney said, noting that virologists here are interested in how EBV contributes to both B cell cancers (lymphomas) and epithelial cell cancers (nasopharyngeal carcinoma and gastric carcinoma).

“Though the EBV-initiated epithelial cell cancers are relatively rare here, they’re more common across other parts in world,” Kenney added.

As for HPV, research from the lab of Paul Lambert, PhD, has recently developed significant new mouse models to study HPV-induced carcinogenesis, or the formation of cancer, in cervical, anal and head and neck cancers. This model has proven to be a productive resource for investigating how natural HPV infection contributes to different types of human cancer and for testing new therapies.

In addition, virology research at UW and beyond also plays a key role in the prevention of disease. Much like research into SARS-CoV-2 led to the development of highly effective vaccines against COVID-19, virology research is also directly responsible for the development of the HPV vaccine, which protects young people against several viral-induced cancers, including cervical, penile, vaginal and vulvar. There’s also a safe and effective Hepatitis B vaccine, which can prevent the virus from attacking the liver and potentially causing liver cancer.

It all started with virology research in the lab. And while UW’s virology program has traditionally been made up of laboratory scientists, program leadership has branched out in recent years to recruit more members with a clinical background, allowing homegrown science to come to life in both the clinic and clinical trials.

That includes the program adding their first surgeon to the roster: Evie Carchman, MD.

“She’s started a special clinic to concentrate on how to treat anal cancer that’s caused by papillomavirus,” Kenney said. “She’s also recently received some grants to try new therapies, including topical treatments that might be less toxic than the current therapies.”

Maintaining a strong foundation of basic science while pushing the boundaries of what’s possible in the clinic – it’s an important evolution for the program, but it’s also one that UW’s cancer virologists are well equipped to handle.

“We’ve seen tremendous advances in terms of prevention and treatment of virally induced cancers, and we’re just getting started.” Kenney said. “We really think we’re one of the best virology programs in the world.”