A serious complication for cancer patients undergoing treatment are blood clots that block major blood vessels, preventing oxygen and nutrients from reaching vital organs. Such clots are the second-leading cause of death for cancer patients, and they may be caused by chemotherapy, researchers at the University of Otago report.
Their study, “Mechanistic insight into the procoagulant activity of tumor-derived apoptotic vesicles,” published in Biochimica et Biophysica Acta (BBA) – General Subjects, shows that chemotherapy treatment stimulates the release of tiny lipid bubbles from the surface of cancer cells, which may be responsible for the formation of these blood clots.
A link between cancer and thrombosis (blood clot formation) was seen more than 100 years ago, and chemotherapy is now associated with a six- to seven-fold increased risk of thrombosis. But why such a link exists has confounded scientists.
A team led by Alex McLellan, a microbiology and immunology associate professor at the New Zealand university, found that when cancer cells are treated with chemotherapy, they release lipid-rich vesicles with procoagulant properties.
“We now have insight into how these bubbles from dying cancer cells may cause thrombosis during chemotherapy,” McLellan said in a press release.
The investigators looked for interactions with known coagulant factors, to assess if these could explain the procoagulant properties of the vesicles released by the cancer cells. Although the vesicles were seen to contain the coagulation Factor V, its presence wasn’t a major contributor to the rapid clotting caused by the bubbles, the researchers determined. Instead, the team found that the over-abundance of clotting lipids and the Tissue Factor protein were responsible.
“Since cancer-induced coagulation events also encourage tumour progression, our work opens up the possibility of developing inhibitors to the major coagulation pathway identified in cancer cells. The coagulation factors identified may be the Achilles heel of the cancer. Our current work is exploiting these molecules as targets for cellular and drug-based therapies,” McLellan said.
Importantly, researchers also found that patients with solid tumors, like pancreatic, lung, or brain cancers, are more likely to experience thrombosis than those with lymphoma.
The researchers stressed that the benefits of chemotherapy clearly outweigh its possible risks, and that such results should not discourage patients from receiving treatment. Instead, they believe that it is important to identify patients at higher risk of thrombosis so they might managed in ways that reduce such risk.