The Multifaceted Metabolism of Glioblastoma

Abstract

Glioblastoma multiforme (GBM) develops on glial cells and is the most common, as well as the deadliest, form of brain cancer [1]. As in pancreatic cancers, distinct combinations of genetic alterations in GBM subtypes induce a multiplicity of metabolic phenotypes, which explains the variability of GBM sensitivity to current therapies targeting its reprogrammed metabolism. Therefore, it is becoming imperative for cancer researchers to account for the metabolic heterogeneity within this cancer type before making generalized conclusions about a particular drug’s efficacy against all cancers of that type. GBMs can be classified initially into two subsets consisting of primary and secondary GBMs, and this categorization stems from cancer development. GBM is the highest grade of gliomas, which includes glioma I, glioma II, glioma III, and glioma IV (GBM). Secondary GBM develops from a low-grade glioma to advanced stage cancer, while primary GBM provides no signs of progression and is identified as an advanced stage glioma from the onset. The differences in prognosis and histology correlated with each classification are normally negligible, but the demographics of individuals affected and the accompanying genetic/metabolic properties show distinct differentiations [2].

GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets

“…The Warburg effect, despite having been conceptualized by Otto von Warburg over 100 years ago, has received renewed interest of late in the search for valid drug targets in solid tumors including diffuse gliomas [41,42,43]. This strategy of chemotherapeutic drug development allows for the avoidance of extremely morbid side effects seen with most other chemotherapies.…”

Glioblastoma multiforme: Metabolic differences to peritumoral tissue and IDH‐mutated gliomas revealed by mass spectrometry imaging

“…7 While major metabolic changes in tumors include enhanced aerobic glycolysis, so-called the Warburg effect, and glutamine metabolism, 9,10 genomic and epigenetic alterations also modulate the metabolism in GBM. 11,12 The analysis of the GBM metabolism is gaining interest to improve diagnostic accuracy and to promote therapeutic effects. 13,14 Molecular spectroscopy and mass spectrometry (MS) are common tools for the investigation of metabolites and metabolic alterations.…”

“…Other common molecular GBM markers like p53, phosphatase and tensin homolog (PTEN), phosphoinositide 3‐kinase (PI3K), epidermal growth factor receptor (EGFR), and 1p/19q have an ambiguous prognostic importance 7 . While major metabolic changes in tumors include enhanced aerobic glycolysis, so‐called the Warburg effect, and glutamine metabolism, 9,10 genomic and epigenetic alterations also modulate the metabolism in GBM 11,12 . The analysis of the GBM metabolism is gaining interest to improve diagnostic accuracy and to promote therapeutic effects 13,14 …”

Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks

“…Despite these novel pieces of evidence suggesting a role of S1P in tumor metabolic aberrations, further studies are needed to explore this less-studied aspect of S1P signaling. In this context, it is worth mentioning that, among different metabolic deregulations, aberrant lipid metabolism has emerged as crucial, not only as an energy source and in providing substrates for membrane synthesis, but also for its role in cellular signaling in both GBM cells and GSCs [307,308]. Concerning lipid signaling, different studies demonstrated that lysophosphatidic acid (LPA), a major membrane-derived lipid-signaling molecule beside S1P, acts as a key player in GBM [309,310].…”