Cancer consists of heterogeneous cells, including cancer stem cells (CSCs), cancer cells, and tumor-associated cells, such as immune cells and vascular cells. Considering that these diverse cell types influence one another directly and indirectly through membrane proteins and secretion factors, such as exosomes and growth factors, the overall heterogeneity affects tumorigenicity and resistance to therapy. This review explores cancer heterogeneity, focusing on CSC heterogeneity, and discussed how the heterogeneity emerges by the intrinsic mechanism and the external factors and affects response to therapy. Additionally, as a potential therapeutic strategy to address this heterogeneity, I propose new Adeno-associated virus carrying a miRNA-dependent CSC eradication system that targets all types of CSCs with minimizing side effects.

Glioblasoma (GBM), GBM-initiating cells (GICs), heterogeneity, stem cell factors, microRNA (miR), Adeno-Associated virus (AAV)