Endocrine Abstracts

High-grade astrocytomas (HGAs) remain the most prevalent and malignant brain tumor based on its locally aggressive behavior, being glioblastoma (grade-IV astrocytoma) the most lethal. The current standard treatment for glioblastomas consists of surgery followed by radiotherapy and/or chemotherapy. However, the average period of survival is about 14 months after the first intervention. Therefore, there is a clear clinical need for the identification of novel diagnostic, prognostic and therapeutic tools to manage and treat these brain pathologies. In this context, somatostatin analogues (SSAs) are efficacious and safe treatments for a variety of endocrine related tumors, but the presence of somatostatin receptors (SSTRs) and pharmacological effects of SSA on HGAs are poorly known. Specifically, we have recently reported that the truncated splicing variant of SSTR5, sst5TMD4, is overexpressed and associated with increased aggressiveness in glioblastomas. In this study, we demonstrated that the expression levels of the 5 canonical receptors (SSTR1-5) were significantly down-regulated in HGAs compared to non-tumor samples using different human cohorts (both internal and external cohorts). Notably, SSTRs expression levels were inversely correlated with the tumoral grade, and, consequently, with the aggressiveness of HGAs. Moreover, ROC curve and survival analysis demonstrated the potential value of SSTRs, mainly SSTR1 and SSTR2, as novel diagnostic and prognostic biomarkers. Additionally, lower expression levels of SSTRs were associated with aggressive parameters (i.e., IDH wildtype status, classical/mesenchymal subtypes, etc.) showing a potential pathophysiological role of the somatistatin-system in HGAs. Notably, treatment with different SSAs (octreotide, pasireotide) and specific receptor-agonists (SSTR1/SSTR2/SSTR5 agonists) significantly reduced cell proliferation in primary patient-derived glioblastoma cell cultures. Altogether, this study demonstrated that SSTRs expression is dysregulated in HGAs vs. control brain tissues and could represent a novel souse of diagnostic and prognostic biomarkers, since their expression is associated with critical clinical and pathological features. Moreover, our data unveil clear antitumoral effects of SSAs on HGAs, opening new avenues to explore their potential as targeting therapy for these devastating brain pathologies.