P2, N=208, Recruiting, BioVie Inc. | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Nov 2025 --> Jun 2026

Canonical NF-κB signaling is mechanistically related to UM cell survival, proliferation, and migration, as shown by pharmacologic inhibition like BAY11-7082, and niclosamide and genetic modulation like microRNA-9. NF-κB signaling, particularly the canonical branch, is required for UM malignancy, while noncanonical signaling is linked with high-risk features. Branch-specific genetic manipulations and clinically relevant models should be employed in future research to maximize therapeutic strategies.

P1/2, N=24, Active, not recruiting, University of Nebraska | Trial primary completion date: Dec 2025 --> Jul 2026

To investigate the involvement of the NF-κB signaling pathway, HCT116 cells were treated with the NF-κB inhibitor Bay 11-7082...Mechanistically, TFPI-2 knockdown inhibited ferroptosis by promoting NF-κB pathway activity. This study reveals that TFPI-2 suppresses CRC progression by inducing ferroptosis through NF-κB signaling, providing new insights for future CRC therapy.

This mechanism can be effectively inhibited by silencing CXCR2 or by employing the NF-κB inhibitor BAY 11-7082...Additionally, in EC tissue samples, CXCL1 and CXCR2 expression, as well as the extent of macrophage infiltration, exhibited a significant positive relationship with disease progression, suggesting an unfavorable prognosis. In conclusion, targeting the CXCL1/CXCR2 axis is a potential therapeutic approach for EC treatment.

GSDME functions as a tumor suppressor by enhancing radiosensitivity and inhibiting proliferation and migration in ESCC, through the suppression of the NF-κB signaling pathway. These findings nominate GSDME as a promising biomarker and the NF-κB signaling pathway as a therapeutic target for overcoming radioresistance in ESCC.

In contrast, NRF2 activators, such as bardoxolone methyl (CDDO-Me), sulforaphane, and dimethyl fumarate, exhibit chemopreventive effects by enhancing detoxification and mitigating oxidative DNA damage during early tumorigenesis...Therefore, understanding the temporal and contextual effects of NRF2 signaling is crucial for therapeutic design. The aim of this review is to examine how pharmacological modulation of NRF2 influences the invasive and metastatic dimensions of tumor progression, in addition to discussing its potential integration into TNM-based prognostic and treatment frameworks.

Similarly, subcutaneous KEAP1 KO tumors were larger and more immune-suppressed compared to WT tumors. Both CDDO-Me and omaveloxolone reduced the tumor burden and improved immune cell phenotypes within the TIME independent of KEAP1 mutational status.

RNA-seq analysis was also utilised to highlight the molecular mechanisms underpinning the effects DOX in AC16 cells and the CDDO-mediated mitigation of cardiotoxicity. This study provides novel insight into NRF2 dynamics in the widely utilised AC16 cells whilst further elucidating the molecular mechanisms contributing to DOX cardiotoxicity and potential NRF2-orchestrated defence.

Differentiated adipocytes were used for (1) treatment with 0, 5, 10, or 15 ng/mL of GH for 8 h, or 15 ng/mL of GH for 0, 4, 8 or 12 h; (2) co-treatment with 15 ng/mL GH and 0.1 ng/mL tumor necrosis factor α (TNF-α); (3) pretreatment with 10 μM BAY 11-7082, a nuclear factor kappa B (NF-κB) inhibitor, and then treatment with 15 ng/mL GH...Furthermore, TNF-α exacerbated GH-induced lipolysis and inflammation, whereas inhibition of NF-κB signaling pathway partially reverses these metabolic alterations of GH-treated adipocytes. These findings suggested that GH promote lipolysis in bovine adipocytes by activating inflammatory pathways.

P1/2, N=50, Recruiting, Tanta University | Not yet recruiting --> Recruiting | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2025 --> Nov 2026

A nuclear factor-kappa B (NF-κB) inhibitor, BAY11-7082, and a cyclooxygenase 2 (COX2) inhibitor, celecoxib, significantly inhibited PGE2 secretion, indicating that NF-κB and COX2 played a crucial role in reovirus-induced PGE2 production. These results indicate that reovirus replication in tumor cells is important for reovirus-induced PGE2 production. Attention should be paid to possible PGE2 production in tumors following reovirus treatment.