In this context we are currently interested in the physiological, pharmacological and toxicological functions of:
- ATP binding cassette (ABC) multidrug transporters
- Organic Anion Transporting Polypeptides (OATPs)
- Cytochrome P450 3A proteins
- Carboxylesterases
We are specifically interested in the involvement of these broad-specificity detoxifying drug-transporting and drug-metabolizing systems in:
- Multidrug resistance and susceptibility of tumor cells to anticancer drug treatment.
- Oral bioavailability of anticancer and other drugs.
- Tissue distribution, excretion, and toxicity risks of anticancer and other drugs.
- Drug-drug interactions.
- Protection from dietary, environmental, and pharmacotherapeutic carcinogens.
- Protection from naturally occurring xenotoxins.
- Physiological functions and effects apart from the detoxifying roles, with an emphasis on homeostatic roles of the liver.
- Possibilities to pharmacologically modulate the activity of these detoxifying systems in order to improve pharmacotherapy of cancer and other diseases.
- Inter- and intra-patient variability in therapeutic efficacy and toxicity risks of drugs as a consequence of gene polymorphisms, inhibition or induction of the detoxifying systems.
These research questions are primarily studied in vivo using knockout and transgenic mouse models that are usually generated in the group, as well as in vitro in cell lines or inside-out membrane vesicles overexpressing one or more of the transporters and/or metabolizing enzymes.
Insights from our work, as well as the developed models, turn out to be very useful during the development of new drugs, allowing better prediction of in vivo drug behavior.