Researchers identified new strategies for aggressive glioblastoma treatment

At the University of Tartu, in the research laboratory of the Department of Hematology and Oncology, new drug candidates were identified that could prove effective against the aggressive tumour, glioblastoma.

According to a member of the research team, Associate Professor in Oncology Jana Jaal, glioblastoma is the most aggressive malignant tumour in adults and it is therefore extremely important to study possible new treatments and find more effective treatment combinations. “There is no cure for glioblastoma patients and despite long-term research, the survival rate of this disease has not been significantly improved so far. Surgical removal of the tumour has been the standard treatment of glioblastoma for decades. The postoperative radiation therapy and chemotherapy have been administered since 2005, but despite that, the patients live approximately 14 months only,” Jaal explained.

In the course of the study, researchers identified new drug candidates, enzyme Aurora A inhibitors, which could prove particularly efficient in the treatment of this aggressive tumour. “In the research laboratory of the Department of Hematology and Oncology of the Institute of Clinical Medicine, University of Tartu, we have tried to systematically analyse the modulation of a set of signalling pathways in glioblastoma. We used different cell lines of glioblastoma and 13 drugs and drug candidates that blocked enzymes and receptors essential for the development of the glioblastoma. We also developed a microscopy-based method that enabled, using an automated data analysis algorithm, to count the cell number on plate and assess the extent of DNA damage in the cell nuclei,” said Head of Research Laboratory Darja Lavõgina. Researchers also discovered that azacytidine in combination with lomustine, the standard chemotherapy agent, could significally improve the efficacy of treatment.

Jana Jaal added that the new treatments identified in this study could be further tested in clinical research. “The combination of azacytidine and lomustine seems particularly attractive because both drugs have been used in clinical practice for a long time – azacytidine for haematological tumours and lomustine for the treatment of recurrent glioblastoma. The side effects and safety profile of these two drugs are well known and this would allow phase II clinical trials to be carried out immediately,” Jaal explained. “Aurora A inhibitors should also definitely be studied further because among all the tested drugs, specifically this treatment proved to be the most promising in monotherapy.”

The research was carried out as part of a base financed project of the Institute of Clinical Medicine, University of Tartu. The article “Viability fingerprint of glioblastoma cell lines: roles of mitotic, proliferative, and epigenetic targets” was published in Scientific Reports, a Nature journal

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