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The effect of the tyrosine kinase inhibitor tirabrutinib on anthracycline resistance in a tumor cell line.
Lebeková, Nikola ; Wsól, Vladimír (advisor) ; Matoušková, Petra (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Nikola Lebeková Supervisor: prof. Ing. Vladimír Wsól, Ph.D. Title of diploma thesis: The effect of tyrosine kinase inhibitor tirabrutinib on anthracycline resistance in a cancer cell line Malignancies represent a broad spectrum of heterogeneous diseases caused by genetic and epigenetic alterations that negatively affect various human tissues, contributing to the development of malignancy. Chemotherapy is considered one of the main pillars in the treatment of malignant diseases. Anthracycline chemotherapeutics are widely used drugs in these indications. However, adverse effects resulting from their mechanism of action are a major obstacle. The role in the development of cardiotoxicity, as one of the adverse effects of therapy, is played by carbonyl reducing enzymes that produce toxic reduced metabolites by conferring metabolic reduction of anthracyclines. At the same time, these metabolites show significantly lower cytotoxic activity, thus contributing to the formation and further development of resistance, another severe obstacle in clinical practice. This thesis aimed to investigate the inhibitory effect of a specific tyrosine kinase inhibitor tirabrutinib at the cellular level. The...
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