Glioblastoma heterogeneity and cancer cell plasticity

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor. It represents one of the deadliest human cancers, with an average survival at diagnosis of about 1 year. This poor prognosis is due to therapeutic resistance and tumor recurrence after surgical removal. One of the most important hallmarks of GBM is tumor heterogeneity. Intertumor heterogeneity is mostly characterized by distinct genetic alterations that occur in individual tumors originating in the same organ and allows the classification of these tumors into different molecular subtypes. Intratumor heterogeneity—the diversity within individual tumors—has become the focus of research interest in the past few years, and tumor cell plasticity as a new source of cancer stem cells has added another level of complexity to this phenomenon. This review describes the molecular heterogeneity of GBMs at the transcriptome level and the expression profile–based classification of histopathologically indistinguishable tumors into different subtypes. In addition, the role of dedifferentiation of tumor cells into a stem cell–like state is discussed as a source of cellular heterogeneity within tumors, highlighting tumor cell plasticity as an important driver of GBM heterogeneity. Understanding tumor heterogeneity will help design better therapies against GBM and avoid tumor recurrence.