The project focused on characterising the cell cycle state (proliferating and quiescent) cancer stem cells (CSCs) are present in glioblastoma multiforme (GBM) and their different contribution to tumor formation, progression, and relapse after therapy. Indeed, the main problem of incurability of GBM is due to the recurrence within 6-9 months after first treatment. Furthermore, the invasive feature makes GBM to be completely removed by surgery. In the past, several studies have attempted to demonstrate what is the role of quiescent cancer cells in the progression and relapse of the disease after therapy but their role in cancer invasion remain unclear. Even if believed such cells are indeed responsible for the incurability of GBM, the clear scientific confirmation needed a new method or tool specifically designed to do so. The project aimed to address such biological questions using an innovative method developed ad hoc for studying CSCs from a cell cycle point-of-view. Indeed, in the previous studies, the lack of proper tools to specifically trace or ablate or in general to focus the investigation on quiescent cells might have contributed to the poor knowledge on their contribution in GBM pathogenesis. The knowledge obtained from this project is important for society because, due to the lack of an efficient therapy, it will be used to identify new therapeutical target to fight aggressive brain cancers. The main results showed the presence of quiescent cells where the cancer cells invade brain, and their functional characterization highlighted their importance for the invasion and spreading of cancer. In addition, we developed a new model of brain cancer using cerebral organoids. This will allow scientific community to use also artificial mini brain cancer to investigate several biological questions reducing the need of animals.
