Abstract
Glioblastoma (GB), also known as grade IV astrocytoma, represents the most aggressive form of brain tumor, characterized by extraordinary heterogeneity and high invasiveness and mortality. Thus, a great deal of interest is currently being directed to investigate a new therapeutic strategy and in recent years, the research has focused its attention on the evaluation of the anticancer effects of some drugs already in use for other diseases. This is the case of peroxisome proliferator-activated receptors (PPARs) ligands, which over the years have been revealed to possess anticancer properties. PPARs belong to the nuclear receptor superfamily and are divided into three main subtypes: PPAR-α, PPAR-β/δ, and PPAR-γ. These receptors, once activated by specific natural or synthetic ligands, translocate to the nucleus and dimerize with the retinoid X receptors (RXR), starting the signal transduction of numerous genes involved in many physiological processes. PPARs receptors are activated by specific ligands and participate principally in the preservation of homeostasis and in lipid and glucose metabolism. In fact, synthetic PPAR-α agonists, such as fibrates, are drugs currently in use for the clinical treatment of hypertriglyceridemia, while PPAR-γ agonists, including thiazolidinediones (TZDs), are known as insulin-sensitizing drugs. In this review, we will analyze the role of PPARs receptors in the progression of tumorigenesis and the action of PPARs agonists in promoting, or not, the induction of cell death in GB cells, highlighting the conflicting opinions present in the literature.
Highlights
Glioblastoma (GB) is the most common and aggressive subtype of malignant brain tumors
A detailed analysis was carried out in order to summarize the role of the peroxisome proliferator-activated receptors (PPARs) receptor family in GB, a brain tumor characterized by high aggression
Most investigations have shown that PPAR-β/δ activation is related to tumor progression, whereas PPAR-α and PPAR-γ are associated with antitumor action [84]
Summary
Glioblastoma (GB) is the most common and aggressive subtype of malignant brain tumors. Secondary GB constitutes 5% of cases and develops from astrocytomas with a lower degree of malignancy, affects younger patients and is related to mutations in isocitrate dehydrogenase 1 and 2 (IDH 1 and 2) and tumor protein 53 (P53) [7]. It is a tumor characterized by an extraordinary intra-tumoral heterogeneity which often results in the inability of traditional therapies to obtain long-term remissions. Glioblastomas, differ in phenotypic properties, including transient quiescence, self-renewal, adaptation to hypoxia, and resistance to therapy-induced DNA damage For this reason, the development of new personalized treatment strategies for GB represents both a preclinical and clinical challenge [8]. The purpose of this review is to summarize the role of PPARs in GB, focusing on the antitumor action of their synthetic and natural ligands, in order to consider them as potential additional treatments to conventional therapies
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