Studium farmakokinetických a farmakodynamických mechanizmů lékové rezistence a jejich modulace u nemalobuněčného plicního karcinomu

Zhang, Yu

Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Pharmacology and Toxicology Doctoral Degree Program Pharmacology and Toxicology Candidate Yu Zhang Supervisor Assoc. Prof. RNDr. Jakub Hofman, Ph.D. Advisor Title of Doctoral Thesis Study of pharmacokinetic and pharmacodynamic mechanisms of drug resistance and their modulation in non-small cell lung cancer Lung cancer represents one of the most threatening malignancies, which is attributed by its leading morbidity and mortality among all cancer types. Pharmacological interventions have played impressive roles in the clinical management of non-small cell lung cancer (NSCLC) with the outstanding improvements on patients' survival. Nevertheless, the inevitable emergence of drug resistance severely diminishes their efficacies. Traditional chemotherapeutic drugs have been introduced in the treatment of NSCLC decades ago. Countless studies showed that the emergence of multidrug resistance (MDR) is deeply associated with two pharmacokinetic factors: (1) increased drug efflux via ATP-binding cassette (ABC) transporters and (2) enhanced drug deactivation by biotransformation enzymes, e.g., cytochromes P450 (CYPs). Previously, we and others have demonstrated that several novel targeted agents can synergistically...

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