Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies

Glioma represents the most prevalent primary tumors of the central nervous system, originating from glial cells. Cancer stem cells have the ability to extensively proliferate, self-renew, and form colonies, which contribute to tumorigenesis. Studies have found a population of cells within glioblastoma exhibiting characteristics similar to those of cancer cells, termed glioma stem cells (GSCs). GSCs have two distinct phenotypes: mesenchymal subtype (MES) and proneural subtype (PN). Despite the vital role of these subtypes in glioma biology, there is a significant lack of comprehensive reviews focusing on the regulatory mechanisms underlying each phenotype.This review integrates emerging insights into the regulatory mechanisms underlying GSCs plasticity, with dedicated analysis of novel pathways governing PN and MES phenotypes and their dynamic transition. By examining these critical elements, we aim to contribute to the development of novel therapeutic strategies in the ongoing fight against gliomas.