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<p>Glioblastoma remains an incurable tumour (median survival: ~ 15&#xa0;months) and little clinical progress has been made over the past decades. Therefore, identification of novel biomarkers and therapeutic targets is imperative. Targeting the somatostatin/cortistatin-system is considered a successful avenue for treating different tumour pathologies. Thus, we comprehensively characterized (clinically and molecularly) the expression of the somatostatin/cortistatin-system components [ligands and receptors (SSTRs)] using five cohorts of patients and tested the <i>in-vitro</i> therapeutic response of different SSTR-agonists&#xa0;and somatostatin analogs (SSAs) in primary patient-derived glioblastoma cells. A clear downregulation of the whole somatostatin/cortistatin-system (except for SSTR5) in glioblastoma <i>vs</i>. non-tumour brain samples was demonstrated, with high discriminatory capacity. Moreover, poor overall-survival and critical aggressiveness-parameters (<i>i.e.,</i> recurrence, <i>IDH1</i>-wildtype and G-CIMP status, classical and mesenchymal GBM-subtypes, <i>EGFR</i>-amplification) were robustly associated with SSTR1/SSTR2 downregulation. Notably, octreotide, pasireotide, and SSTR1/2/5-agonists treatments significantly reduced cell-proliferation in primary patient-derived GBM-cells. Molecularly, antitumour effects of octreotide/pasireotide were exerted through key signalling-factors related to glioblastoma-aggressiveness (<i>i.e.,</i> CDKN1A-B/JAK-STAT/NF-κB/TGF-β-pathways). Altogether, this study demonstrated that somatostatin/cortistatin-system is drastically altered in GBM representing a useful prognostic tool, and that SSTR-modulators might represent a potential therapeutic strategy to treat specific subsets of patients with GBM.</p>

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Assessing the diagnostic, prognostic, and therapeutic potential of the somatostatin/cortistatin system in glioblastoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月23日

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  • Miguel E. G-García,
  • Ana S. De la Rosa-Herencia,
  • Álvaro Flores-Martínez,
  • María Ortega-Bellido,
  • Rafael Sánchez-Sánchez,
  • Cristóbal Blanco-Acevedo,
  • Manuel D. Gahete,
  • Juan Solivera,
  • Raúl M. Luque,
  • Antonio C. Fuentes-Fayos

摘要

Glioblastoma remains an incurable tumour (median survival: ~ 15 months) and little clinical progress has been made over the past decades. Therefore, identification of novel biomarkers and therapeutic targets is imperative. Targeting the somatostatin/cortistatin-system is considered a successful avenue for treating different tumour pathologies. Thus, we comprehensively characterized (clinically and molecularly) the expression of the somatostatin/cortistatin-system components [ligands and receptors (SSTRs)] using five cohorts of patients and tested the in-vitro therapeutic response of different SSTR-agonists and somatostatin analogs (SSAs) in primary patient-derived glioblastoma cells. A clear downregulation of the whole somatostatin/cortistatin-system (except for SSTR5) in glioblastoma vs. non-tumour brain samples was demonstrated, with high discriminatory capacity. Moreover, poor overall-survival and critical aggressiveness-parameters (i.e., recurrence, IDH1-wildtype and G-CIMP status, classical and mesenchymal GBM-subtypes, EGFR-amplification) were robustly associated with SSTR1/SSTR2 downregulation. Notably, octreotide, pasireotide, and SSTR1/2/5-agonists treatments significantly reduced cell-proliferation in primary patient-derived GBM-cells. Molecularly, antitumour effects of octreotide/pasireotide were exerted through key signalling-factors related to glioblastoma-aggressiveness (i.e., CDKN1A-B/JAK-STAT/NF-κB/TGF-β-pathways). Altogether, this study demonstrated that somatostatin/cortistatin-system is drastically altered in GBM representing a useful prognostic tool, and that SSTR-modulators might represent a potential therapeutic strategy to treat specific subsets of patients with GBM.