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A groundbreaking study has revealed that blood clots in cancer patients may originate in response to signals from the lungs rather than from other organ sites, as previously believed. The study, conducted by researchers at Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, and the University of California San Diego Health, was recently published in Cell.
Blood clots, the second leading cause of death among cancer patients with advanced disease, can obstruct circulation and cause life-threatening complications. Normally, clotting occurs to prevent excessive bleeding from injuries, but cancer patients often develop clots without any apparent injury. The study suggests that tumors drive this process by releasing chemokines—secreted proteins that travel to the lungs and prompt immune cells called macrophages to release small vesicles. These vesicles then interact with platelets, leading to clot formation.
A New Understanding of Thrombosis in Cancer
“This work redefines the concept of how thrombosis develops in cancer patients,” said Dr. David Lyden, lead researcher and professor at Weill Cornell Medicine. “It’s a revolutionary concept that thrombosis is initiated in the lung, which wasn’t appreciated before.”
Co-senior authors Dr. Diane Simeone, director of Moores Cancer Center at UC San Diego Health, and Dr. Jacqueline Bromberg, a breast medical oncologist at Memorial Sloan Kettering Cancer Center, emphasized the importance of these findings. “Many of our patients with cancer are at high risk for blood clots,” said Dr. Bromberg. “Our study helps unravel the causes of this phenomenon and the potential development of tests and therapeutics for these high-risk patients.”
Tumors and Their Role in Clot Formation
The research team reviewed post-mortem studies and found that up to 60% of cancer patients died due to blood clots rather than cancer itself. “It is unfortunate because we have drugs that can prevent clots, but we can’t give them unconditionally to all patients due to the risk of excessive bleeding,” said first author Dr. Serena Lucotti of Weill Cornell Medicine.
Through experiments in mice and human tissues, researchers discovered that different cancers release varying levels of the chemokine CXCL13. While breast cancer and melanoma release lower levels, they can still trigger clot formation if they metastasize to the lungs. Pancreatic cancer, on the other hand, secretes high levels of CXCL13, affecting lung macrophages even when the tumor is distant.
New Avenues for Treatment and Diagnosis
Further experiments demonstrated that lung macrophages influenced by CXCL13 release vesicles carrying integrin β2, an adhesion molecule that binds to platelets and promotes clotting. An antibody that blocks this interaction successfully prevented clot formation in mice without causing excessive bleeding. Moreover, mice treated with the antibody showed significantly fewer metastases, suggesting a dual benefit in preventing both clotting and cancer spread.
Dr. Lucotti is now working on developing a human antibody to target integrin β2-platelet interactions in patients. Additionally, the research team analyzed blood samples from pancreatic cancer patients and found that integrin β2 levels in extracellular vesicles could serve as a biomarker to predict clotting risk.
“These findings reinforce the idea that cancer is a systemic disease affecting multiple organs beyond the primary tumor site,” said Dr. Lyden. “By understanding and addressing these systemic effects, we may be able to reduce complications and improve patient outcomes.”
Disclaimer: This article is based on a preclinical study and is intended for informational purposes only. While the findings are promising, further clinical research is needed before these insights can be translated into routine medical practice. Patients should consult their healthcare providers for personalized medical advice.
