Glioblastoma biomarkers from bench to bedside: advances and challenges

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.

Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

“…These GBM stem cells (GBSC) are capable of self-renewal and differentiation into neuronal, macroglial, and mixed neuronal/astroglial phenotypes [20]. Recent genome-wide transcriptional analysis identified two phenotypically different subtypes of GBSC, namely, proneural and mesenchymal, which also correlate well with corresponding proneural and mesenchymal signatures in GBMs [21, 22].…”

Establishment and Characterization of Primary Glioblastoma Cell Lines from Fresh and Frozen Material: A Detailed Comparison

“…The main purpose for generating in vitro models of brain tumors is to identify mechanisms contributing to oncogenesis or tumor maintenance starting with analysis of distinct molecular patterns and to define and evaluate potential therapeutic strategies. “Targeted” therapies “only” need molecular testing but for functional analyses such as response prediction vital and proliferating malignant cells are indispensable [6], [7]. On top, they provide a nearly unlimited supply of material for all sorts of studies.…”

ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models

“…Molecular markers have increasingly been used to assess and manage adult malignant gliomas. 5,[13][14][15][16][17] Dozens of proteomics-based approaches have sought to find proteins that are unique to gliomas 11 but have been severely limited by issues of sample size, ability to detect low abundance proteins, and reproducibility. Many of these studies have generated hundreds and even thousands of putative candidates, yet have not been able to follow them up with subsequent validation and characterization.…”