A study of interactions of novel anticancer drugs with drug transporters.

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Aleš Šorf Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of doctoral thesis: A study of interactions of novel anticancer drugs with drug transporters. Despite the significant progress in recent years, the efficiency of anticancer therapy is still complicated by drug resistance. This phenomenon can be mediated by pharmacokinetic mechanisms such as efflux via ATP-binding cassette (ABC) transporters and biodegradation of parent drug to inactive metabolites via metabolizing enzymes. These proteins also play a key role in absorption, distribution and excretion of drugs. When two or more interacting substances are administered simultaneously, the pharmacokinetic drug-drug interactions may occur. Since the targeted protein kinase inhibitors are becoming more common and important component of modern anticancer therapy, the aim of this study was to elucidate interactions of selected drugs of this novel therapeutic group with ABC transporters and also drug metabolizing enzymes by in vitro approaches. We further examined relevant substances ex vivo using mononuclear cells isolated directly from the blood of patients de novo diagnosed for acute myeloid leukemia (AML). Regarding the..