image: Charles Spruck, Ph.D. view more
Credit: Sanford Burnham Prebys
LA JOLLA, CALIF. April 25, 2023 - With the help of a new grant from the U.S. Department of Defense for more than $1.7 million, Associate Professor Charles Spruck, Ph.D., will advance an innovative therapeutic approach for metastatic prostate cancer. Known as viral mimicry, the approach tricks the body into thinking that it has a viral infection, stimulating an immune response that can help the body fight cancer.
“In viral mimicry, the body thinks there’s an infection, which kicks the immune system into high gear,” says Spruck. “With the immune system activated, cancer cells are more responsive to treatment, and tumor growth slows. All of this can happen without triggering treatment resistance, which could be a huge benefit for treating prostate cancer.”
Prostate cancer is the second most diagnosed cancer in men worldwide and the fifth leading cause of cancer death among men. According to the World Health Organization, there were an estimated 1.4 million new cases of prostate cancer and more than 375,000 deaths from the disease in 2020 alone.
“Many cases of prostate cancer are treatable, so people don’t think of it as a major public health issue,” says Spruck. “But when prostate cancer becomes metastatic or resistant to therapy—such as hormone therapy—it can ultimately become a fatal disease. One of the benefits of this approach is that it works in a completely different way, so it’s not as susceptible to resistance.”
The new approach takes advantage of a bizarre evolutionary feature of our genomes called endogenous retroviruses (ERVs). These are small sequences in our genomes, left behind by viruses that infected our ancient ancestors. ERVs have been found in the genomes of early humans such as Neanderthals, but are thought to have first emerged in animals hundreds of millions of years ago, well before there were any humans. Unlike regular viruses, ERVs do not make us sick. Instead, they bounce around our genomes and help control gene expression.
“ERVs are inactive, so they don’t produce proteins the way regular genes do,” says Spruck. “In this study, we discovered that we can reactivate these viruses selectively in cancer cells and essentially fool the body into thinking it needs to trigger an immune response against the tumor.”
Spruck’s team has already discovered a potential drug that can induce viral mimicry in prostate cancer cells. However, the drug is not potent or selective enough to enter the clinic. One of the goals of their project is to develop more potent compounds that can induce viral mimicry, which could lay the foundation for tomorrow’s prostate cancer treatments.
“Something very exciting about this work is that it has the potential to move to the clinic extremely quickly,” says Spruck. “We hope to have a drug ready for the clinic within three years.”
In addition to prostate cancer, the viral mimicry approach could be effective across a range of treatment-resistant cancers. The researchers are already exploring the approach in ER+ breast cancer in which up to 50% of patients experience a relapse due to treatment resistance.
“We initially discovered viral mimicry in breast cancer, and we suspected it could work in other cancers,” says Spruck. “This project is helping us see how far we can take this unique approach, and I’m confident we’ll be able to apply it more broadly in the future as we continue to learn more about how it works.”
The grant is titled “A Viral Mimicry Approach to Target Prostate Cancer (HT9425-23-1-0135).”
About Sanford Burnham Prebys
Sanford Burnham Prebys is an independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 45 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children’s diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us at SBPdiscovery.org or on Facebook facebook.com/SBPdiscovery and on Twitter @SBPdiscovery.