Cleveland Clinic researchers uncover how virus causes cancer, point to potential treatment

Cleveland Clinic researchers have discovered a key mechanism used by Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), to induce cancer. The research points to effective new treatment options for KSHV-associated cancers, including Kaposi’s sarcoma, primary effusion lymphoma, and HHV8-associated multicentric Castleman disease.

“Our findings have significant implications: viruses cause between 10% to 20% of cancers worldwide, a number that is constantly increasing as new discoveries are made. Treating virus-induced cancers with standard cancer therapies can help shrink tumors that are already there, but it doesn’t fix the underlying problem of the virus,” said Jun Zhao, Ph.D., of Cleveland Clinic Florida Research & Innovation Center. “Understanding how pathogens transform a healthy cell into a cancer cell uncovers exploitable vulnerabilities and allows us to make and repurpose existing drugs that can effectively treat virus-associated malignancies.”

The Nature Communications study, led by Dr. Zhao, reveals that KSHV manipulates two human enzymes called CDK6 and CAD to reshape the way human cells produce new nucleotides - the building blocks of DNA and RNA - and process glucose. The changes to how infected cells grow and how KSHV persists put cells at a much higher risk of forming tumors and play a crucial role in causing cancer. 

The team showed the virus activates a specific pathway driving cell metabolism and proliferation. Inhibiting this process with existing FDA-approved breast cancer drugs reduced KSHV replication, blocked lymphoma progression and shrunk existing tumors in preclinical models. 

KSHV-induced cancers are fast-acting, aggressive and difficult to treat. An estimated 10% of people in North America and Northern Europe have KSHV, but this ranges throughout the globe. More than 50% of individuals in parts of Northen Africa are estimated to have the virus. Experts estimate these rates are higher, as KSHV often goes undiagnosed because of lack of symptoms. These findings have implications that reach past KSHV; researchers can apply knowledge about KSHV to other cancer-associated viruses that might use the same process to cause cancer.

March 4, 2024