The NFκB pathway: a therapeutic target in glioblastoma

Abstract

Cancer initiating cells have been described to be the only cell population with tumorigenic capacity in glioblastoma multiforme, one of the most aggressive and untreatable cancers. Recent work from our group described that NFκB pathway was activated in glioblastoma initiating cells undergoing differentiation, and that blockade of this activation promoted senescence of differentiating cells. NFκB activation in cancer may be the result of either exposure to proinflammatory stimuli in the tumor microenvironment or upregulation of the signaling pathway by upstream regulators. Appropriate control of NFκB activity, which can be achieved by gene modification or pharmacological strategies, would provide a potential approach for the management of NFκB related tumors, including glioblastoma. Here, we summarize the current knowledge of the relevance of NFκB in cancer and its possible role as a target of therapeutic intervention.

A DNA Methylation Prognostic Signature of Glioblastoma: Identification of NPTX2-PTEN-NF-κB Nexus

“…Although the association between NF-kB pathway activation and GBM aggressiveness and chemoresistance as well as NF-kB as a therapeutic target is known (24,28), our study clearly shows that NF-kB pathway is activated particularly in high-risk group. Our data also show that NF-kB inhibition could sensitize only those glioma cells having activated NF-kB pathway to chemotherapy.…”

Butein impairs the protumorigenic activity of malignant pleural mesothelioma cells

“…17,18,23,24 In addition, several NFκB-and STAT3-small-molecule inhibitors have been identified, and some of them are undergoing preclinical evaluation. 28 However, we believe that the use of butein in this experimental study has several advantages compared with other inhibitors. First, butein appears to target both NFκB and STAT3 (Fig.…”

“…25 In line with this, pharmacological inhibition of NFκB or STAT3 increases the sensitivity of many solid and non-solid tumors to radio-and chemotherapy. [26][27][28] In this paper, we aim to test whether the interference with both NFκB and STAT3 activation Chronic inflammation appears to be a driving force behind cancer progression. NFκB and StAt3 activation plays a pertinent role in this process by mediating chemoresistance and the acquisition of mesenchymal features of protumorigenic cells.…”

A novel NFIA-NFκB feed-forward loop contributes to glioblastoma cell survival

“…[15][16][17][18] NFκB activation in cancer may be the result of either exposure to pro-inflammatory stimuli, such as tumor necrosis factor (TNF), or upregulation of signaling from upstream regulators. [19][20][21][22] NFκB is constitutively active in many cancers, including gliomas, [23][24][25] and aberrant regulation of NFκB signaling is involved in apoptosis evasion and tumor promotion. 26 In GBM, elevated NFκB signaling is associated with enhanced chemo-and radiation resistance in the mesenchymal subtype.…”