Researchers at Cleveland Clinic have identified a crucial mechanism employed by Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), to induce cancer. This breakthrough points towards potential new treatment options for KSHV-associated cancers, including Kaposi’s sarcoma, primary effusion lymphoma, and HHV8-associated multicentric Castleman disease.
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Cleveland Clinic
The study, led by Dr. Jun Zhao at Cleveland Clinic Florida Research & Innovation Center, highlights how KSHV manipulates human enzymes CDK6 and CAD to alter the production of nucleotides and glucose processing in infected cells. These changes significantly increase the risk of tumor formation and play a crucial role in causing cancer.
The virus activates a specific pathway governing cell metabolism and proliferation. Inhibiting this process using FDA-approved breast cancer drugs in preclinical models demonstrated a reduction in KSHV replication, blocked lymphoma progression, and shrank existing tumors.
KSHV-induced cancers are particularly challenging to treat and are associated with fast-acting and aggressive tumor growth. The virus can remain dormant in the body, but reactivates in high-risk groups, triggering aggressive cancers. The findings have broader implications beyond KSHV, as they provide insights into other cancer-associated viruses that might employ similar processes to induce cancer.
Collaborating with Dr. Michaela Gack, Scientific Director of the Florida Research & Innovation Center, Dr. Zhao’s team uncovered how the virus takes over host proteins to enhance metabolism, facilitating faster viral replication and uncontrolled cell proliferation.
In preclinical models, the team treated tumors with a CDK6-blocking drug, Palbociclib, and a compound targeting CAD. The results were promising, with significant decreases in tumor size and improved cancer survival rates. The researchers plan to further refine their experimental drug combinations for future clinical trials.
Dr. Zhao emphasized the significance of understanding the metabolic rewiring mechanisms employed by viruses and cancers, aiming to identify vulnerabilities that could lead to more effective treatments. This breakthrough offers hope for developing targeted therapies against virus-induced cancers and has the potential to impact cancer research beyond KSHV.
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