Research News

Thrombosis is one of the leading causes of mortality for people with cancer and is a common side effect of cancer treatment, with approximately 30% of venous thrombosis cases occurring in cancer patients. Platelets typically respond to injury as part of the repair process, but at times can clog up a vein, causing venous thrombosis.

Recently published research from Cleveland Clinic, featured in Circulation Research, sheds light on how tumors release particles into the bloodstream, stimulating the formation of blood clots. The discovery paved the way for a new preventive strategy against thrombosis, involving patent-pending antibodies, currently in development at Cleveland Clinic. The antibodies hinder the interactions between platelets and tumor-derived small extracellular vesicles (sEVs), tiny particles that tumors dispatch into the bloodstream to carry cancer-related genetic material.

The study, first authored by Tejasvi Dudiki, PhD, outlines this process in the context of prostate, breast and renal cancer. SEVs are also associated with coagulation abnormalities in many other conditions, including COVID-19 and other cancers, says Tatiana Byzova, PhD, senior author on the paper and staff in Neurosciences.

Platelets are crucial tools for our immune system, not only forming protective barriers but also signaling to the immune system that it's time to repair an injury. The receptors present on cancer-sEVs bind with receptors on platelets, facilitating the entry of cancer-sEVs into the platelets. This interaction triggers platelet activation, which in turn prompts platelet aggregation and clot formation.

Antibodies developed in Dr. Byzova's lab block off the protein on the cancer-sEV's surface that interacts with a receptor on the platelet, which prevents platelets from binding to the cancer-sEVs. The goal: preventing thrombosis and other conditions that stem from cancer-sEVs uptake. The antibodies are currently in pre-clinical development.

The study also explored platelets as a source of biomarkers for tumor presence in prostate cancer patients, underscoring the potential diagnostic value of platelet analysis. The researchers observed that around 70% of patients exhibited a specific prostate cancer marker accumulating in their platelets. But this accumulation disappeared after successful treatment involving the removal of the prostate gland.

Thrombosis also helps cancers metastasize, making it more difficult to treat. The elevated risk of clotting alone complicates treatment, as patients with cancer are also more susceptible to bleeding and hemorrhage. Conventional treatments like blood thinners contribute to this risk, highlighting the critical need for the development of novel therapeutic approaches.

"Finding a balance between preventing blood clots and maintaining appropriate hemostasis is crucial to ensure patient safety," says Dr. Byzova, whose lab specializes in the vascular system and preserving its health. "A more targeted approach is also essential for tailoring therapies to vulnerable patients, like older people who are more at risk for heart conditions."