Roles of STAT3 in the pathogenesis and treatment of glioblastoma

Abstract

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.

Association of immunoglobulin E levels with glioma risk and survival

“…Intriguingly, some forms of HIES have been shown to arise from dominant negative mutations in the signaling transduction and activator of transcription 3 (STAT3) gene 27 , which has been linked to many cancers including glioma 28,29 . While the role of STAT3 and the JAK/STAT pathway has been well studied in IDH-WT GBMs [30][31][32] , its significance in IDH-MT glioma is less clear. Further research is needed to investigate the etiologic role of IgE in gliomagenesis, its interaction with genomic alterations and its potential as a therapeutic intervention.…”

Τ cell-mediated adaptive immunity in the transition from metabolic dysfunction-associated steatohepatitis to hepatocellular carcinoma

“…On the contrary the correction of STAT-3 enhanced signaling, repressed tumor incidence irrespective of T cell recruitment, MASH, and fibrosis ( Grohmann et al, 2018 ). Interestingly, a growing body of evidence renders STAT-3 signaling a pivotal mechanism in developing various malignancies ( Poser et al, 2019 ; Fu et al, 2023 ). Grohmann et al highlights that the recruitment of T cells and the development of MASH and fibrosis are not mandatory for developing HCC in obesity.…”

Next Generation of Brain Cancer Nanomedicines to Overcome the Blood–Brain Barrier (BBB): Insights on Transcytosis, Perivascular Tumor Growth, and BBB Models

“…[ 87 ] In addition, studies have shown that IL‐6 induces a reciprocal STAT3 activation loop, where IL‐6 released from GBM cells stimulates STAT3 activation which, in turn, results in the upregulation of IL‐6 generation in the astrocytes within the tumor microenvironment. [ 88 ] This enhanced IL‐6 level further activates STAT3 in GBM cells, promoting tumor growth, apoptosis resistance, migration, and invasion. [ 88 ] As such, these findings indicate that targeting STAT3 via IL‐6 could potentially be used as an approach to suppress GBM invasion and tumor growth.…”

“…[ 88 ] This enhanced IL‐6 level further activates STAT3 in GBM cells, promoting tumor growth, apoptosis resistance, migration, and invasion. [ 88 ] As such, these findings indicate that targeting STAT3 via IL‐6 could potentially be used as an approach to suppress GBM invasion and tumor growth. For instance, Chen et al have recently developed polyglycerol‐nano‐diamonds loaded with the anticancer drug DOX, which were specifically designed to target glioma cells while simultaneously inhibiting STAT3 activation and reducing their IL‐6 expression from astrocytes.…”

“…For instance, Chen et al have recently developed polyglycerol‐nano‐diamonds loaded with the anticancer drug DOX, which were specifically designed to target glioma cells while simultaneously inhibiting STAT3 activation and reducing their IL‐6 expression from astrocytes. [ 85b ] The produced NPs not only efficiently inhibited STAT3/IL‐6 activation in GBM cells but also disrupted the reciprocal activation loop between GBM cells and astrocytes, leading to tumor inhibition upon administration to U87 GBM‐bearing mice.…”