Developing animal-free methods to study thrombosis in cancer patients.

Cancer-associated thrombosis-on-a-chip

Cancer patients are at an increased risk of developing thrombosis, but the reasons for this are currently unknown. Although the mechanisms leading to thrombosis in cancer patients have been studied in animals such as mice, animals do not spontaneously develop thrombosis and are a poor model to study why cancer patients develop thrombosis. Therefore, Leiden University Medical Center and Mimetas B.V., a leading company in producing alternatives to animal experimentation, have teamed up to develop an animal-free model that can be used to study the mechanisms that drive cancer-associated thrombosis.

Cancer-associated thrombosis causes great discomfort to the cancer patient, causes the oncologist to stop cancer treatment, and is the second cause of death in cancer patients. Treatment of thrombosis in cancer patients raises the costs of health care with 50% and is thus very costly. Therefore, a better understanding of cancer-associated thrombosis, which processes cause cancer-associated thrombosis and how it could be prevented are of great importance. Development of a model that better mimics human disease is therefore warranted.

To develop this model, they used an existing organ-on-a-chip platform designed by Mimetas B.V., the OrganoPlate® Graft. Their cancer-associated thrombosis-on-a-chip model includes a tumor spheroid and a vessel compartment. Blood plasma containing blood clotting factors was perfused through the blood vessels to study whether and how fast the presence of a tumor spheroid led to blood clotting and thrombosis. Using this model, they also tested which clotting factors and which tumor-expressed genes influenced the speed of blood clotting.

The results showed that their platform can detect the activation of blood coagulation promoted by tumor spheroids. It is also able to evaluate the effect of anticoagulant drugs and tumor-expressed genes effects. The platform has the potential to accelerate the discovery of new drugs. Additionally, it could also be employed as a tool for personalised medicine.

Summary
Cancer patients have a higher risk to develop thrombosis but the reasons for this are unknown. Animal models are not suited to study this. Therefore, in this project new models will be developed to study the mechanistic and genetic basis of thrombosis in cancer patients.
Technology Readiness Level (TRL)
2 - 3
Time period
24 months
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