Signal transducer and activator of transcription 3 (Stat3) is a key signaling protein driving major hallmarks of cancer and represents a promising target for the development of targeted glioblastoma therapies.
The interplay between glioblastoma and microglia cells leads to endothelial cell monolayer dysfunction via the interleukin-6-induced JAK2/STAT3 pathway.
Evidences from both preclinical and clinical studies have demonstrated that STAT3 plays a critical role in several malignancies associated with poor prognosis such as glioblastoma and triple-negative breast cancer, and STAT3 inhibitors have shown efficacy in inhibiting cancer growth and metastasis.
Neutralizing antibody against BTC abrogated activation of both EGFR and NF-ᴋB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in glioblastoma cells.
According to the results of both in vitro and in vivo assays, a combined therapy of LV‑STAT3 siRNA with AZD0530 could enhance therapeutic effects on glioblastoma, supporting the idea that the combination of LV‑STAT3 siRNA and AZD0530 could serve as a novel and effective strategy to combat glioblastoma.
On multivariate analyses with the COX proportional hazards regression model including pY705-Stat3 expression, age and relapse status, pY705-Stat3 status was an independent prognostic factor in glioblastoma (P < 0.001).
Western blot analysis revealed elevated SHP-1 expression and reduced phosphorylated (p)-STAT3 expression in glioblastoma cells treated with VB compared with controls.
The importance of signal transducer and activator of transcription 3 (STAT3) signaling in the growth and survival of glioblastoma cells has been well documented, while the reasons leading to STAT3 activation remains to be elucidated.