Since the 1960s it is known that many platinum complexes possess anticancer activity. At the same time, extensive studies of cell cycle regulation mechanisms during the last decades have led to a new strategy in cancer treatment - consisting of the inhibition of cyclin-dependent kinases (Cdks). Iryna Stepanenko, who has been rewarded the Hertha-Firnberg grant recently, works on platinum group metal-based Cdk inhibitors.

The scientific interest of Dr. Iryna Stepanenko has always focused on compounds of platinum group metals and their unique physical-chemical properties. During her PhD at the Institute of General and Inorganic Chemistry at the Ukrainian National Academy of Sciences in Kiev she investigated their potential as high-performance catalysts. Later, the use of platinum metal group compounds in biological and medical research was so exciting for her that she decided to contact one of the leading bioinorganic chemists who is known for anticancer research: Univ.-Prof. DDr. Bernhard Keppler from the Institute of Inorganic Chemistry of the University of Vienna.

Since the year 2004, Iryna Stepanenko is a member of the team of the research platform "Translational Cancer Therapy Research" that is led by Bernhard Keppler. The goal of the research group is to develop new metal-based medications to fight cancer tumors. We talked with Iryna Stepanenko after she received a project fund within the Hertha-Firnberg-Programme of the Austrian Science Fund (FWF).

Redaktion: What does the Hertha-Firnberg grant mean to you?
Stepanenko: It is an excellent opportunity to work in the fast-developing field of chemotherapy. Fighting cancer is of world-wide importance. In industrialized countries cancer has the second highest mortality after cardio vasculardiseases. In 2007, nineteen thousand patients died of cancer in Austria. The Hertha-Firnberg grant gives me a chance, if you like, to be useful to society.

Redaktion: What is your research about?
Stepanenko: Traditionally, organic compounds dominated among the different chemotherapeutic agents. Interest in the anticancer platinum complexes started with the discovery that a platinum compound, cisplatin, possesses antitumor properties. This 'pushed' metal complexes into a new field of potential applications. So a huge amount of them was synthesized and tested for anticancer activity. The main goal of my project is to synthesize platinum metal group-based complexes with organic compounds (viz. Cdk inhibitors), which are themselves active against cancer.

Redaktion: Why is the regulation of Cdk activity a priority approach in cancer therapy?
Stepanenko: Cyclin-dependent kinases (Cdks) are a group of enzymes which are responsible for DNA replication and for the whole cell cycle regulation. Cancer is characterized by out-of-control growth of abnormal cells and overactivity of the cell cycle Cdks. Therefore agents that are capable to modulate the cell cycle and lead to the cell death, like Cdks inhibitors, might be used to treat cancer.

Redaktion: Why are metal-based therapeutic agents particularly useful?
Stepanenko: The key target for cancer chemotherapy is DNA. The group of platinum metal complexes has attracted considerable attention mainly because of their direct DNA binding. To target the DNA of a tumor cell is highly desirable and can be achieved via the regulation of tumor-selective uptake and increasing the drug affinity of its ultimate target.

Redaktion: What can be expected from the metal-based Cdk inhibitors you are working on?
Stepanenko: A growing number of organic Cdk inhibitors is in clinical evaluation. In our group we have been studying the effect of metalation on the biological properties of Cdk inhibitors (paullones) for four years. We succeeded to overcome the insufficient solubility and bioavailability of paullones which hamper their potential medical application. The binding of Cdk inhibitors to metallic moieties can preserve or even enhance their antitumor activity.

Redaktion: How do you experience your scientific life in your lab?
Stepanenko: I am working in an interdisciplinary team and therefore I have a lot of possibilities for a fruitful exchange of ideas. The access to up-to-date instrumentation and experimental techniques of this laboratory, as well as to the most recent literature is an excellent basis for my ongoing research. My daily work on the new Hertha-Firnberg-project until now is the synthesis of the known 'imidazolyl pyrazole Cdk inhibitors'. The research of anticancer activity of the new platinum metal complexes is planned in collaboration with the Institute of Cancer Research, Medical University of Vienna, the Max-Planck Institute of Biochemistry, Martinsried, Germany and the Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno. (hh)


The project "Novel metal-based Cdk Inhibitors for anticancer therapy" is funded by the FWF within the Hertha-Firnberg Programme and runs from 1.10.08 to 30.09.11.