Examination of possible applications of direct thrombin inhibitors in the therapy of colon cancer

Program "Pokreni se za nauku", Phillip Morris Company, 2020-2021
Principal Investigator: Dr Branko Tomic, IMGGE
Participants from IMGGE: Dr Maja Gvozdenov, Marija Cumbo, Srdjan Boskovic

A malignant tumor of the colon annually affect over one million people around the world and is one of the leading causes of death associated with cancer. Despite numerous studies and progress in understanding the molecular mechanisms that lead to colon cancer, current therapeutic options are limited, especially for patients with progression and metastasis. Intertwined nature of the malignant tumor and blood coagulation is known for more than 150 years and the increasing number of data points to coagulation factors also shows that they can play a role in tumorigenesis. Current research shows the role of one of the key regulators in blood coagulation (thrombin), in the growth and progression of tumors, and was detected in the tumor microenvironment in tissues in which the physiological conditions are not synthesized. Our preliminary research results on the in vitro system of cell lines originating from human colon tumors, indicates a possible role of thrombin in the development of neoplastic changes. The assumption is that the uses of direct thrombin inhibitors (group of new anticoagulants) prevent further development and complications of tumor. The aim of this research was to in vivo, in the model zebrafish (Danio rerio), examine whether the extent and the direct acting thrombin inhibitors on tumor cells and that may affect some of their properties (growth, division, migration). This project will be used several types of cell lines originating from human colon tumors, metastatic potential and different characteristics. Fluorescently labeled tumor cells will be examined by injecting the transplanted zebrafish, a model system allows assessment of the angiogenic potential and metastatic cancer cells. Thus formed xenografts model system will be treated with the selected direct thrombin inhibitors, to the clinical response in vivo tumor cells. If the result reveals that the direct inhibitors of thrombin may affect tumor cells, this could significantly contribute to the further test access to the treatment of humans suffering from malignant tumors. By applying appropriate therapy may be a decrease in mortality due to colon cancer and complications during treatment, as with other types of tumors.