Glioblastoma (grade IV glioma according to the World Health Organization) is the most malignant and aggressive brain tumor. It arises de novo in 95% of the cases and is then called a primary glioblastoma. Patient outcomes are poor: the median overall survival is only 20 months after diagnosis despite optimal therapy (maximal safe tumor resection, radiotherapy, temozolomide chemotherapy and magnetic tumor-treating fields) in the fittest patient populations.
In many tumor types, including glioblastoma, cancer cells with stem cell characteristics have been described and are called cancer stem cells (CSCs). CSCs are slowly-dividing or non-dividing cells expressing effective DNA repair and multidrug resistance mechanisms that enable survival of CSCs after radiotherapy and chemotherapy and regrowth of the tumor. CSCs are resistant to therapy because of their surrounding tumor microenvironment or “niche”, which comprises of the cells and tissue structures that help to enforce the stem cell characteristics on CSCs. In glioblastoma tumors, glioma stem cells (GSCs) reside in niches in which they are maintained in a slowly-dividing or quiescent state. Radiotherapy and chemotherapy have their optimal efficacy in proliferating cells, which means that quiescent GSCs escape from the effects of therapy in their protective niches. Almost two decades ago, the concept of the CSC niche was introduced in glioblastoma research. It was argued that GSC niches are crucial for maintaining the stem cell characteristics and quiescence of GSCs in the tumors, that render GSCs resistant to therapy and cause recurrence of the tumor after treatment . This raises the question whether the standard treatment modalities for glioblastoma can be improved by targeting GSC niches in glioblastoma tumors that are responsible for therapy resistance and tumor recurrence.
The project is performed in a collaboration with the Biotechnical Faculty of the University of Ljubljana (Dr. Miloš Vittori, Dr. Urban Bogataj) and the Institute of Cell Biology of the Medical Faculty of the University of Ljubljana (Prof. Dr. Peter Veranič, Prof. Dr. Mateja Erdani-Kreft and Prof. Dr. Rok Romih).
This project is financed by the Slovenian Research and Innovation Agency (ARIS).
Project ID: ID: J3-2526
Duration: 1.9.2020―31.8.2023
