Combined Targeting of Glioblastoma Stem-Like Cells by Neutralizing RNA-Bio-Drugs for STAT3

Esposito, Carla Lucia; Nuzzo, Silvia; Ibba, Maria Luigia; Ricci–Vitiani, Lucia; Pallini, Roberto; Condorelli, Gerolama; Catuogno, Silvia; Franciscis, Vittorio de

doi:10.3390/cancers12061434

Cited by 13 publications

(6 citation statements)

References 58 publications

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“…GL21.T, an inhibitor ligand specific for receptor tyrosine kinase (RTK) Axl, is often used to target miR-10b, and we found that combined treatment with Gint4.T-STAT3 and GL21.T-anti-miR-10b complexes significantly abrogated the proliferation of GSCs. Here we found that the combined treatment of Gint4.T-STAT3 with GL21.T-10b resulted in a synergistic and drastic inhibition of GSC self-renewal (Esposito et al, 2020).…”

Section: Sirnas Targeting Stat3mentioning

confidence: 65%

Roles of STAT3 in the pathogenesis and treatment of glioblastoma

Hou²,

Dong³

et al. 2023

Front. Cell Dev. Biol.

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Glioblastoma (GBM) is the most malignant of astrocytomas mainly involving the cerebral hemispheres and the cerebral cortex. It is one of the fatal and refractory solid tumors, with a 5-year survival rate of merely 5% among the adults. IL6/JAK/STAT3 is an important signaling pathway involved in the pathogenesis and progression of GBM. The expression of STAT3 in GBM tissues is substantially higher than that of normal brain cells. The abnormal activation of STAT3 renders the tumor microenvironment of GBM immunosuppression. Besides, blocking the STAT3 pathway can effectively inhibit the growth and metastasis of GBM. On this basis, inhibition of STAT3 may be a new therapeutic approach for GBM, and the combination of STAT3 targeted therapy and conventional therapies may improve the current status of GBM treatment. This review summarized the roles of STAT3 in the pathogenesis of GBM and the feasibility of STAT3 for GBM target therapy.

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Section: Sirnas Targeting Stat3mentioning

confidence: 65%

Roles of STAT3 in the pathogenesis and treatment of glioblastoma

Hou²,

Dong³

et al. 2023

Front. Cell Dev. Biol.

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“…Inhibition of STAT3, which functions both as a signal transducer and transcription factor, may also improve outcomes in GBM. Small interfering RNAs targeting STAT3 can reduce the GSC population in vitro and tumor growth in vivo [ 247 ]. Small molecule inhibitors of the STAT3 pathway include Stattic, which targets the SH2 domain of STAT3, and WP1066, which suppresses STAT3 activity and prevents its phosphorylation [ 123 , 248 ].…”

Section: Targeted Therapymentioning

confidence: 99%

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Hersh

Gaitsch

Alomari

et al. 2022

Cancers

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Glioblastoma (GBM) is an aggressive tumor of the central nervous system categorized by the World Health Organization as a Grade 4 astrocytoma. Despite treatment with surgical resection, adjuvant chemotherapy, and radiation therapy, outcomes remain poor, with a median survival of only 14-16 months. Although tumor regression is often observed initially after treatment, long-term recurrence or progression invariably occurs. Tumor growth, invasion, and recurrence is mediated by a unique population of glioblastoma stem cells (GSCs). Their high mutation rate and dysregulated transcriptional landscape augment their resistance to conventional chemotherapy and radiation therapy, explaining the poor outcomes observed in patients. Consequently, GSCs have emerged as targets of interest in new treatment paradigms. Here, we review the unique properties of GSCs, including their interactions with the hypoxic microenvironment that drives their proliferation. We discuss vital signaling pathways in GSCs that mediate stemness, self-renewal, proliferation, and invasion, including the Notch, epidermal growth factor receptor, phosphatidylinositol 3-kinase/Akt, sonic hedgehog, transforming growth factor beta, Wnt, signal transducer and activator of transcription 3, and inhibitors of differentiation pathways. We also review epigenomic changes in GSCs that influence their transcriptional state, including DNA methylation, histone methylation and acetylation, and miRNA expression. The constituent molecular components of the signaling pathways and epigenomic regulators represent potential sites for targeted therapy, and representative examples of inhibitory molecules and pharmaceuticals are discussed. Continued investigation into the molecular pathways of GSCs and candidate therapeutics is needed to discover new effective treatments for GBM and improve survival.

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“…The treatment of patient-derived GSC lines with the Gint4.T-STAT3 AsiC in combination with a chimera containing the anti-Axl aptamer GL21.T conjugated to an antagonist for microRNA (miR)-10b (GL21.T-10b) efficiently inhibited tumor sphere formation of GSCs, cell propagation, and invasion. 92,93 Recently, using differential cell-SELEX, Affinito et al 94,95 described a 2 0 F Py-modified RNA aptamer that selectively binds patientderived GSCs but not the same cells grown as adherent cells. The aptamer, named A40s, targets EphA2 on the cell surface of GSCs, inhibiting tumor growth stemness and migration.…”

Section: Targeting Cscsmentioning

confidence: 99%