Making Peace with Cisplatin
Resistance to cisplatin during cancer treatment endangers the lives of patients. Associate Professor Ceyda Açılan Ayhan of the Koç University School of Medicine and KUTTAM (Koç University Research Center For Translational Medicine) is working on reversing this resistance.
Cisplatin is an effective chemotherapy agent that is widely used in the clinical treatment of many different types of cancer. While the success rate of ensuring survival in testicular cancer was initially 10 percent, this rate increased to 85 percent with the use of drugs containing Cisplatin as the active ingredient. In children with medulloblastoma, the addition of this active ingredient to the treatment regimen increased the disease-free survival period by 85 percent. However, some patients can develop drug resistance to cisplatin or are intrinsically unresponsive to cisplatin.
It is vital to resensitize the cells to such a drug. And this is the point of origin for Prof. Ayhan's work.
Prof. Ayhan describes her work as follows; "Because cancer cells divide more frequently than normal cells and because their DNA repair mechanisms do not work as well as normal cells, they die as a result of cisplatin treatment. On the other hand, cancer cells are able to develop resistance to the drug by finding ways to reverse the effect of how it works. One way of doing this is to prevent its uptake into the cell or ensure its expulsion from the cell. In our work, we focused on the expulsion of cisplatin. By combining cisplatin with other drugs, we are trying to prevent the expulsion of drug that is supposed to kill the cancer cells."
Within the scope of the project, the researchers are planning to reduce this expulsion in cancer cells that have developed cisplatin resistance through lysosomal exocytosis, by using targeted drugs towards epigenetic modifiers and thus resensitizing the cells, for the first time. In this context, they are also investigating the molecular mechanisms, which aid in reversing the resistance. The use of epigenetic drugs in cancer treatment is quite novel. This project aims to expand their field of usage, as the first study to identify epi-drugs that may resensitize cells to cisplatin.
Prof. Ayhan and her team identified a few molecules in the early stages of their study, and they will now try to reverse cisplatin resistance by repeating these results. At the same time, they are also working on new drugs that have not yet been used in clinical studies.
When the project is successfully completed, the researchers will have new epi-targeted drug molecules to reverse the resistance to cisplatin, one of the most commonly used chemotherapy agents in clinical applications, and the identification of how these new molecules work. This way, they will have determined the epigenetic factors playing a role in the expulsion of drugs out of the cell via lysosomal exocytosis as well.
Funded for three years
Prof. Ayhan's project received funding of 45,000 Euros for three years from the ICGEB (International Centre for Genetic Engineering). One Ph.D. student (Barış Sergi) and two expert researchers (Dr. Buse Cevatemre, Dr. Hamza Syed) are currently working on the project. Professor Kirill Kiselyov of the University of Pittsburgh, an expert on lysosome biology, is also among the collaborators of the project.
This research is still ongoing, and Barış Sergi received an oral presentation award for his findings at the VIII. International Congress of Molecular Medicine.
Provided by Koc University
