Supervisor de Marie Curie: “MagMA” Applying Metabolomics to Unveil follow-up treatment biomarkers and Identify Novel Therapeutic Targets in Glioblastoma
MSCA-IF-2017 Project, Grant Agreement Number 799378
Glioblastoma multiforme (GBM) is a malignant tumour originating from glial cells. It is the most common and devastating form of malignant brain tumour, containing self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumour initiation and therapeutic resistance. It leads to 225,000 deaths per year in the entire world. Standard treatment consists of maximal surgical resection, followed by radiotherapy with or without concomitant and adjuvant Temozolomide. Such treatment hardly increases patient survival and leads to a median overall survival of only 12–18 months.
By contrast, to other types of cancers, it appears uncertain that GBM incidence can be decreased by changing certain environmental factors, or anticipated from the presence of another disease or condition. Until date, all efforts that have been done to improve patient’s life have shown low efficacy and the survival of such patients has not improved much in the last 60 years. Therefore, it seems clear that new methods for diagnosis, prognosis and treatment are needed.
To better understand GBM tumour biology, several groups worldwide have turned to high dimensional profiling studies. On 2018 Verhaak and collaborators described several GBM phenotypes; Proneural, Neural, Classical and Mesenchymal, each with distinguishing hallmark mutations, copy number alterations, epigenetic alterations, and clinical features. Additionally, treatment efficacy differs per subtype. Nevertheless, a full metabolomic profile had not been performed until date.
The first objective of our study was to investigate the underlying metabolic differences between the most extreme phenotypes (Proneural and Mesenchymal). These generate a characteristic fingerprint, not yet reported until now, thereby providing a better understanding of glioma biology. This finding could help in the development of new strategies to fight the tumour and lead to more personalized therapy.
Another difficulty of GBM is that both, confirmation and follow up of the tumour process are restricted by anatomical location. Nevertheless, neural cells are able to release extracellular vesicles (EVs), which cross the blood-brain barrier and could be detected within the blood, offering a potential new way for detection and treatment monitoring. The second objective of the project was to study the metabolic profile of the EVs released by those subtypes. This research effort has helped to draw the EVs metabolome and to elucidate whether or not the metabolites are directly packaged into specific EVs and their possible function in the surrounding cells. Moreover, it gives the opportunity of finding a metabolite profile characteristic of tumour subtype that could be used as a biomarker.
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“MagMA” Applying Metabolomics to Unveil follow-up treatment biomarkers
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