Glioblastoma: An Update in Pathology, Molecular Mechanisms and Biomarkers

Abstract

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular pathogenesis and biology of this tumor in the past decade, the prognosis for GBM patients remains poor. GBM is characterized by aggressive biological behavior and high degrees of inter-tumor and intra-tumor heterogeneity. Increased understanding of the molecular and cellular heterogeneity of GBM may not only help more accurately define specific subgroups for precise diagnosis but also lay the groundwork for the successful implementation of targeted therapy. Herein, we systematically review the key achievements in the understanding of GBM molecular pathogenesis, mechanisms, and biomarkers in the past decade. We discuss the advances in the molecular pathology of GBM, including genetics, epigenetics, transcriptomics, and signaling pathways. We also review the molecular biomarkers that have potential clinical roles. Finally, new strategies, current challenges, and future directions for discovering new biomarkers and therapeutic targets for GBM will be discussed.

Keywords: biomarkers; epigenetics; genetics; glioblastoma; histopathology; molecular pathology; signaling pathway; transcriptomics.

Figure 1

Integrated histological and molecular classification of the major diffuse gliomas by WHO.

Figure 2

Schematic representation of the key signaling pathways altered in GBM.