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Abstract
Glioblastoma (GBM) is the most common and devastating primary malignant brain tumor in adults. The past few years have seen major progress in our understanding of the molecular basis of GBM. These advances, which have contributed to the development of novel targeted therapies, will change the paradigms in GBM therapy from disease-based to individually tailored molecular target-based treatment. No validated circulating biomarkers have yet been integrated into clinical practice for GBM. There is thus a critical need to implement minimally invasive clinical tests enabling molecular stratification and prognosis assessment, as well as the prediction and monitoring of treatment response. After examination of data from recent studies exploring several categories of tumor-associated biomarkers (circulating tumor cells, extracellular vesicles, nucleic acids and oncometabolites) identified in the blood, cerebrospinal fluid and urine, this article discusses the challenges and prospects for the development of circulating biomarkers in GBM.
Acknowledgements
The authors would like to thank LS Ange for providing editing assistance and S Di Dio for providing graphical assistance.
Financial & competing interests disclosure
A Idbaih has received travel funding from Hoffmann-LaRoche. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
The past decade has seen remarkable strides forward in the genomic characterization of glioblastoma. Several candidate oncogenic alterations have been identified for rational drug design.
Accurate molecular diagnosis is a major issue in precision medicine to assess patient candidacy for a smart therapy targeting specifically molecular alterations in the tumor.
Circulating biomarkers can be collected from blood, urine and cerebrospinal fluid in patients with glioblastoma. Potential applications for such tools encompass early diagnosis, molecular stratification, prognosis assessment, prediction of treatment response and disease course monitoring.
Circulating tumor cells can be isolated and characterized from a simple blood test and their molecular characterization can inform diagnosis, prognosis and therapeutic response.
Cell-free circulating tumor DNA represents a promising biomarker with several potential applications from molecular diagnosis to disease monitoring.
Several circulating proteins have been associated with diagnostic, prognostic and predictive values in glioblastoma.
Analytical and clinical validation of technologies is required if circulating biomarkers are to become routine tests in the clinic; collaborative research efforts worldwide will be decisive in achieving this objective.