Doctoral Dissertation Themes

Study on the role of pharmacokinetic mechanisms in the anticancer drug resistance and possibility of their modulation

Drug resistance represents a critical obstacle to successful anticancer pharmacotherapy. In this work, the role of pharmacokinetic mechanisms (drug transporters and metabolizing enzymes) in tumor drug resistance will be studied. In addition, the possibilities of their modulation to overcome cytostatic resistance will be investigated as well. The student will work with recombinant enzymes, subcelullar fractions, cell lines, primary tumor cultures prepared from patients‘ biopsies and 3D-structured organoids. For the experimental part, number of methods will be employed: proliferation and apoptosis assays; accumulation, transport and enzyme activity assays; immunofluorescence; analysis of gene/protein expression using qRT-PCR/Western-blotting; gene silencing with siRNA or CRISPR/Cas9 and others. This work will shed light on the relevance of pharmacokinetic mechanisms within anticancer drug resistance and provide approaches to overcome it, which may help to significantly improve the pharmacotherapy of cancer patients. The study includes participation in the preparation of grant applications and publications, active attendance of international conferences, and several months of scientific internship abroad. The Research Group of Cancer Pharmacology cooperates closely with hospital clinical oncologists as well as inland and foreign top scientists (USA, Canada, Germany, Sweden). For more information about the research group, please visit https://portal.faf.cuni.cz/Groups/Cancer-Pharmacology/. In addition to the basic doctoral scholarship, the selected candidate will be financially supported by a part-time job on a research grant.

Supervisor: doc. RNDr. Jakub Hofman, Ph.D.

Keywords: cancer, drug resistance, drug transporter, biotransformation enzyme

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