Page 8 - Martin Downs Bulletin - April '24

Page 8, Martin Downs

Cleveland CliniC MarTin healTh news

Minor Head Injuries No Small Cleveland Clinic Researchers KSHV-induced cancers are fast-acting, aggressive
Affair For Seniors Uncover How Virus Causes and difficult to treat. An estimated 10 percent of people
in North America and Northern Europe have KSHV, but

New Treatment For Leaky Blood Vessels In Cancer, Point To Potential this ranges throughout the globe. More than 50 percent
of individuals in parts of Northern Africa are estimated
The Brain Treatment to have the virus. Experts estimate these rates are higher,
as KSHV often goes undiagnosed because of lack of
Any knock to the head, be it from a car accident, slip on Kaposi Sarcoma-Associated Herpesvirus symptoms. These findings have implications that reach
the pickleball court, or fall from a chair, is no small affair. Activates A Specific Pathway To Drive Viral past KSHV; researchers can apply knowledge about
Especially for older adults who experience head trauma. They KSHV to other cancer-associated viruses that might use
are at greater risk of an increasingly common neurological Persistent Infection And Cell Growth, Paving the same process to cause cancer.
condition caused by leaky blood vessels in the brain. The Way For Tumors To Form To understand the cells’ metabolic processes to
Called a subdural hematoma, it occurs when a blow to the uncover the virus’s vulnerabilities, Zhao collaborated with
head tears blood vessels between the brain and the skull. Blood Cleveland Clinic researchers have discovered a Michaela Gack, Ph.D., scientific director of the Florida
then leaks, pools and clots in the space below the dura mater, key mechanism used by Kaposi’s sarcoma-associated Research & Innovation Center.
the outermost layer of three protective membranes surrounding herpesvirus (KSHV), also known as human herpesvirus 8 Rapidly replicating cancer cells reprogram metabolism
the brain. (HHV8), to induce cancer. The research points to effective to fuel growth. Meanwhile, most viruses cannot produce
“A recently published new treatment options for KSHV-associated cancers, energy or necessary molecules on their own, so they rely
study predicts that by 2030, including Kaposi’s sarcoma, primary effusion lymphoma, on human cells to do the work for them. The team found
chronic subdural bleeds will be and HHV8-associated multicentric Castleman disease. that the virus takes over the host protein CDK6 and CAD,
the most common reason for “Our findings have significant implications: Viruses causing the infected cells to produce extra metabolites, which
neurosurgical intervention,” cause between 10 to 20 percent of cancers worldwide, a allows faster replication of the virus and an uncontrolled
said Jeffrey Miller, M.D., a number that is constantly increasing as new discoveries proliferation of the cells.
neuro endovascular surgeon are made. Treating virus-induced cancers with standard The research team treated preclinical models with a
at Cleveland Clinic Martin cancer therapies can help shrink tumors that are already CDK6-blocking drug, Palbociclib, an FDA-approved breast
Health. there, but it doesn’t fix the underlying problem of the cancer medication, as well as a compound targeting CAD.
A New Understanding virus,” said Jun Zhao, Ph.D., of Cleveland Clinic Florida They saw significant decreases in tumor size and increases
Subdural hematomas Research & Innovation Center. “Understanding how in cancer survival rates: Most tumors virtually disappeared
occur in up to 25 percent of pathogens transform a healthy cell into a cancer cell after about a month of treatment, and remaining tumors
people with head injuries, uncovers exploitable vulnerabilities and allows us to shrank around 80 percent. Survival increased to 100 percent
and individuals taking blood make and repurpose existing drugs that can effectively for selected lymphoma cell lines.
thinners are at increased risk. Jeffrey Miller, M.D. treat virus-associated malignancies.” Zhao and his team are working to better understand the
Symptoms may include The Nature Communications study, led by Dr. Zhao, connections among KSHV, CDK6/CAD pathway, and cancer
ongoing headache, confusion and drowsiness, nausea and reveals that KSHV manipulates two human enzymes formation. With the knowledge they obtain, they plan to
vomiting, slurred speech and changes in vision. If the bleeding called CDK6 and CAD to reshape the way human cells implement and refine their experimental drug combinations
occurs slowly enough, the symptoms may not appear for weeks produce new nucleotides – the building blocks of DNA for clinical trials.
or months. As a result, an older person may not even recall and RNA – and process glucose. The changes to how “Cellular metabolism could be hijacked by both viruses
how their head injury happened. infected cells grow and how KSHV persists put cells at and cancers for pathogenesis,” said Zhao. “By investigating
“If someone is experiencing any of these symptoms, it is a much higher risk of forming tumors and play a crucial these metabolic rewiring mechanisms, we aim to find the
always best to be evaluated by a professional,” said Dr. Miller. role in causing cancer. Achilles’ heel of cancer-causing viruses and nonviral cancers.
“If left untreated, subdural hematomas can quickly lead to The team showed the virus activates a specific pathway I’m excited to see what the future of this work holds.”
permanent neurological injury or death.” driving cell metabolism
It is now believed, however, that chronic bleeding into the a n d p r o l i f e r a t i o n .
site of the hematoma may be instead caused by blood leaking Inhibiting this process
from fragile arteries that develop after the injury and initial wi t h e xi st i ng FDA-
blood clot formation. “These new blood vessels feed the approved breast cancer
membrane that forms around the clotted blood,” says Miller. drugs reduced KSHV
Innovative Treatment replication, blocked
This new understanding has led to the development of lymphoma progression
an innovative endovascular treatment for chronic subdural and shrunk existing tumors
hematomas called middle meningeal artery (MMA) in preclinical models.
embolization. Like other herpesviruses,
The middle meningeal artery is a large blood vessel that KSHV often has no symptoms
supplies oxygen-rich blood to the dura mater surrounding the initially and remains in
brain. A flexible tube called a catheter is used to inject a small the body after primary
amount of bioadhesive gel into branches of the artery that lead infection. The virus stays
to the hematoma. This cuts off blood supply to the membrane dormant, suppressed by the
surrounding the hematoma and prevents rebleeding. immune system. However,
The team at Cleveland Clinic Martin Health has KSHV can reactivate when
successfully treated more than 100 patients with this immunity is weakened – as
minimally invasive approach. In addition to being an effective in older people, those with
treatment, patients enjoy a faster recovery and a lower risk HIV/AIDS, and transplant
of complications. recipients. In these high-
To learn more about neurological services at Cleveland risk groups, the now active
Clinic in Florida, visit ClevelandClinicFlorida.org/Neuro or virus can trigger aggressive
call (877) 463-2010 to make an appointment. cancers.

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