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Study on the role of pharmacokinetic mechanisms of drug resistance in new anticancer drugs with focus on solid tumors
Vagiannis, Dimitrios ; Hofman, Jakub (advisor) ; Souček, Pavel (referee) ; Zendulka, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Dimitrios Vagiannis Supervisor RNDr. Jakub Hofman, Ph.D. Title of Doctoral Thesis Study on the role of pharmacokinetic mechanisms of drug resistance in new anticancer drugs with focus on solid tumors Cancer chemotherapy is an important tool for the cure of cancer. Although the development of new anticancer drugs has been rapidly progressing, the phenomenon of multidrug resistance (MDR) continues to be a key issue leading to therapy failure in oncological patients. MDR is based on pharmacodynamic as well as pharmacokinetic mechanisms. Pharmacokinetic MDR includes drug efflux transporters and biotransformation enzymes that decrease the amount of (active form of) a drug in tumors. While the MDR role of transporters has been well understood, the participation of drug metabolizing enzymes is still unclear. This thesis investigates the role of cytochromes P450 (CYPs) in cytostatic resistance. Furthermore, it focuses on the modulation of pharmacokinetic MDR using pharmacokinetic drug-drug interactions of new targeted antitumor drugs. Finally, it aims to confirm the in vitro findings in ex vivo patient-derived tumor explants. In our latest publication, we demonstrate the significant role of...
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Study on the role of pharmacokinetic mechanisms of drug resistance in new anticancer drugs with focus on solid tumors
Vagiannis, Dimitrios ; Hofman, Jakub (advisor) ; Souček, Pavel (referee) ; Zendulka, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate Mgr. Dimitrios Vagiannis Supervisor RNDr. Jakub Hofman, Ph.D. Title of Doctoral Thesis Study on the role of pharmacokinetic mechanisms of drug resistance in new anticancer drugs with focus on solid tumors Cancer chemotherapy is an important tool for the cure of cancer. Although the development of new anticancer drugs has been rapidly progressing, the phenomenon of multidrug resistance (MDR) continues to be a key issue leading to therapy failure in oncological patients. MDR is based on pharmacodynamic as well as pharmacokinetic mechanisms. Pharmacokinetic MDR includes drug efflux transporters and biotransformation enzymes that decrease the amount of (active form of) a drug in tumors. While the MDR role of transporters has been well understood, the participation of drug metabolizing enzymes is still unclear. This thesis investigates the role of cytochromes P450 (CYPs) in cytostatic resistance. Furthermore, it focuses on the modulation of pharmacokinetic MDR using pharmacokinetic drug-drug interactions of new targeted antitumor drugs. Finally, it aims to confirm the in vitro findings in ex vivo patient-derived tumor explants. In our latest publication, we demonstrate the significant role of...
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