Abstract
Glioblastoma (GBM) is the most commonly diagnosed malignant brain tumor in adults. The prognosis for patients with GBM remains poor and largely unchanged over the last 30 years, due to the limitations of existing therapies. Thus, new therapeutic approaches are desperately required. Sphingolipids are highly enriched in the brain, forming the structural components of cell membranes, and are major lipid constituents of the myelin sheaths of nerve axons, as well as playing critical roles in cell signaling. Indeed, a number of sphingolipids elicit a variety of cellular responses involved in the development and progression of GBM. Here, we discuss the role of sphingolipids in the pathobiology of GBM, and how targeting sphingolipid metabolism has emerged as a promising approach for the treatment of GBM.
Highlights
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults
Recent studies have shown sphingosine kinase 2 (SK2) localization to be regulated by the cytoplasmic protein cytoplasmic dynein 1 intermediate chain 1 (DYNC1I1), which is highly downregulated in GBM, with low DYNC1I1 associated with poor patient prognosis [245]
Current challenges in finding effective therapies for GBM include the high degree of tumor heterogeneity, the presence of glioblastoma-like stem cells, and difficulties in drug delivery due to the blood–brain barrier (BBB) and drug efflux, all of which have been extensively reviewed by others [246,247,248,249]
Summary
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults They are highly aggressive tumors resulting in a median survival of less than 15 months from diagnosis, and a five year survival rate of 6.4%–14.0% [1,2,3]. GBM tumors usually present as a large, irregular mass that is heterogeneous in macroscopic appearance, with cystic and gelatinous areas and multifocal hemorrhage, and frequently display extensive necrosis [10]. In addition to these histopathological features, recent advances have allowed GBM to be classified based on gene expression and mutation analysis into different molecular subtypes [8,11,12]. Despite the high degree of phenotypic and molecular heterogeneity observed in GBM, treatment of this disease differs little between patients, and has remained largely unchanged in the last decade
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