Drug resistance is considered a main limit of pharmacotherapy in cancer patients. Inherent resistance is independent on the previous treatment and arises from an individual´s genetic background. This type of resistance can usually be easily overcome by the re-choice of a therapeutic agent(s). In contrast, acquired resistance results from the selection of resistant clones during the continual drug exposure and is much more dangerous due to the presence of aggressive and multidrug-resistant variants. In addition, the progression of the acquired form leads to the development of metastatic tumors, which are deadly in majority of cases.
In our research, we use single gene-transduced and other cellular models to evaluate the role of selected drug transporters and drug-metabolizing enzymes in acquired cytostatic resistance. The impact of results obtained in artificial cell models is further verified in primary cultures and 2D/3D-structured tumoroids derived from healthy individuals´ and cancer patients´ biopsies, respectively. Obtained knowledge can help understand the true role of pharmacokinetic mechanisms in the phenomenon of multidrug resistance. In turn, it can serve as a valuable background for the development of therapeutic strategies for their modulation in oncological patients, who face the frustrating experience with this clinical obstacle.
In another branch, we reveal pharmacokinetic interactions of novel targeted anticancer agents. Subsequently, we investigate whether these interactions could be utilized for combating cytostatic resistance using in vitro, ex vivo and in vivo techniques. We focus predominantly on novel drugs used/intended for the therapy of non-small cell lung cancer and other solid tumors. The findings from this branch can be transformed into the effective and safe drug combination regimens, which can be exploited for the therapy of drug-resistant cancer patients.
In the currently last main research section, we aim to the preparation of cell lines with acquired resistance to the novel targeted anticancer agents. In established drug-resistant models, we search for the important pharmacokinetic as well as pharmacodynamic resistance drivers, with particular focus on the possible role of factors assosicated with extracellular matrix and tumor microenvironment. Again, we investigate mainly drugs used for the therapy of non-small cell lung cancer.
Generally, our team aims to develop and use progressed ex vivo and in vivo preclinical models to increase the likelihood of translating our findings into the clinical practice. Only such approach can bring the benefit to cancer patients in the future.
We actively collaborate with several inland as well as foreign research teams, which allows us to evolve our scientific scope and performance dynamically. We appreciate them and are opened for the establishment of the new ones. If you feel we could make meaningful work together, do not hesitate to contact us.
Currently, we search for PhD students, who feel motivated to join our team and work on our upcoming grant projects. For more information about dissertation topics, please see Doctoral Dissertation Themes | Charles University, Faculty of Pharmacy (cuni.cz) or Témata disertačních prací | Farmaceutická fakulta Univerzity Karlovy (cuni.cz) for foreign or inland candidates, respectively.