Studying the role of quiescent cancer stem cells in gbm development using a novel in vivo cell cycle-based approach
Glioblastoma (GBM) is the most common and aggressive high-grade primary brain tumour in adults. More than 90% of the patients shows recurrence of the disease with a survival of 2 years despite a multitherapeutic approach consisting of a first surgical resection of the brain lesion followed by radio- and chemo-therapy. GBM patients die because of the cancer relapse that evolve becoming not sensitive to the classical therapies. A sub-population of quiescent/slow cycling cancer stem cells (CSCs) has been proposed to be the origin of the cancer relapse. The features and role of that specific population of CSCs within GBM is still not well characterised. The aim of the proposed project is to first clarify the cell cycle state of CSCs within GBM induced in mouse models in addition to their contribution and role in cancer development. To achieve this goal, I will use a cell cycle-based approach together GBM mouse models to: characterise the cell cycle state of CSCs within tumour (Aim 1); analyse the contribution of quiescent and proliferating CSCs during cancer development and their molecular features using a novel cell cycle-based lineage tracing approach (Aim 2); analyse the effect of selective ablation of each CSCs sub-subpopulation in cancer growth a novel cell cycle-based cellular ablation (Aim 3). Using a cell cycle point of view, the obtained results will be fundamental for the definition and the role of the different CSCs co-existing within glioma. In particular, the findings will open new avenue in the study of the role of quiescent or proliferating cells within GBM and give the possibility to others in the field for testing for example which cells contribute to cancer relapse after the initial tumour treatment (mass debulking and following radio- and chemo-therapy) or even design new drugs targeting specific CSC types.