Czech scientists fight brain cancer
Olomouc, March 12th, 2012 - Scientists from the Institute of Molecular and Translational Medicine (IMTM), which was created as a part of the BIOMEDREG project at the Medical Faculty of Palacký University in Olomouc, has made a significant breakthrough in fighting brain cancer. Their study, which has just been published in the prestigious periodical the American Journal of Experimental Medicine, revealed the mechanism by which the cells of one of the most aggressive tumours, so-called glioblastoma, can hinder the therapy commonly used today. The new discovery has also revealed a path that could lead in the future to more effective treatment.
Gliomas with a high degree of malignity, so-called high-grade gliomas, account for approximately half of all primary brain tumours in adults, and the disease is almost always fatal. In the Czech Republic, about 350 patients are diagnosed with glioblastoma annually; despite aggressive treatment, they survive on the average only fourteen months.
Death is mainly caused by the early dissemination of tumour cells (already at the stage when the diagnosis is first made) to a large distance from the primary tumour; this type of tumour also develops rapid resistance to radiotherapy and chemotherapy. Glioblastoma contain a dense vascular network and a high level of protein known as the vascular endothelial growth factor (VEGF), which supports the growth of blood vessels and thus supports the entire tumour.
In order to suppress the growth of glioblastoma as well as other tumours, an antibody called bevacizumab (Avastin) has been used in recent years; it binds VEGF in the tumour, thereby blocking its activity. However, even this treatment has proved to be only temporary.
"It was a mystery why even this promising therapy fails, but our study has helped us to unravel it," explains Professor Jiři Bártek, the most quoted Czech scientist in the field of biomedical sciences. He is in charge of the Integrity of the Genome Department at the Centre for Cancer Research in Copenhagen, Denmark, which has its own laboratory at the Olomouc Institute of Molecular and Translational Medicine. "The existence of cancer stem cells that are able to survive different types of therapy and are probably also responsible for the recurrence of the disease were known. However, their molecular basis was unclear - the mechanism by which the tumour can defend itself," explains Petra Hamerlík, the first author and member of Professor Bártek´s science team. In addition to Olomouc scientists, there are also colleagues in Denmark, USA and at the Institute of Molecular Genetics of the Academy of Sciences in Prague, who have participated in this study.
Professor Bártek´s team found that glioblastoma tumour stem cells can themselves produce VEGF and also use it biologically to enhance their chances of survival, even under conditions of aggressive therapy that includes administering antibodies against VEGF or radiation.
"We have used a chemical that blocks the enzyme activity of the VEGF receptor and thereby disrupts VEGF signalling in cancer stem cells. This strategy will now be developed in preclinical studies in mice with transplanted human glioblastoma, and potentially even in clinical trials,” Bártek describes the next phase of the research.
"This discovery of our scientists is not only an example of fruitful international collaboration, but it may in the future lead to an improvement in prospects for patients suffering from this malignant disease of the brain. The use of small chemical molecules as inhibitors of the VEGF receptor are clinically routinely used in the treatment of renal carcinomas, for example. This is why the clinical potential of this study in glioblastoma is great. What remains a problem is the penetration of low-molecular-weight drugs into the brain through a biological barrier, but we are working hard even on this issue at our institute.” adds Associate Professor Marian HajdUch, Director of IMTM.
The BIOMEDREG project, which provides an umbrella for the establishment of the Institute of Molecular and Translational Medicine at the Faculty of Medicine of Palacký University in Olomouc, is financed by the European Regional Development Fund and the state budget of the Czech Republic through the Operational Programme Research and Development for Innovation.
For more information, see www.imtm.cz