Glioblastoma mounts a spatial self-protective defense through IL-8-driven TSR formation that restricts oncolytic virus spread. IL-8 functions as both a pharmacodynamic biomarker and a therapeutic target, and its inhibition provides a rational strategy to overcome resistance and optimize GBM virotherapy.

In summary, this study suggests that Fn contributes to GC progression by promoting tumor cell migration, MCs recruitment and activation. Simultaneously, the enhanced CXCL8-mediated crosstalk between GC cells and MCs plays a vital role in the pro-cancer effect of Fn.

P1/2, N=60, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2028 --> Oct 2030 | Trial primary completion date: Oct 2025 --> Oct 2027

Meanwhile, SB225002 exerts directly antitumor activity and enhances the radiosensitivity of cervical cancer cells by facilitating DNA double-strand breaks, promoting G2/M phase cell cycle arrest, and inducing apoptosis. In summary, our findings highlight neutrophils inhibition via CXCR2 antagonist as a promising therapeutic strategy to enhance cervical cancer responsiveness to radiotherapy.

Combination treatment with gemcitabine and Navarixin, a CXCR1 inhibitor, significantly reduced expression of CXCR1, CXCL6, and CSC/EMT markers in vitro. In vivo, tumors treated with the combination therapy showed markedly lower CXCR1 and CXCL6 expression than other treatment groups. These findings indicate that the CXCR1 axis supports CSC maintenance in PDAC, and that co-targeting CSC and non-CSC populations may improve therapeutic outcomes.

P1/2, N=340, Completed, AstraZeneca | Active, not recruiting --> Completed

After intrathecal injection of the CXCR2 antagonist SB225002, the rats' pain threshold increased, accompanied by reduced expression of inflammatory factors and reversal of glial cell activation...Transfection with si-CXCR2 led to decreased expression of p-ERK and p-p38 in microglial cells, along with lower TNF-α and IL-1β levels in the cell supernatant. These results indicate that CXCR2 activates spinal glial cells via the ERK/p38 pathway, promoting neuroinflammation, and CPSP, whereas CXCR2 inhibition counteracts these effects and alleviates CPSP.

Pharmacological inhibition of CXCR2 using SB225002, a selective small-molecule antagonist, was evaluated to determine its effects on cell growth, colony formation, apoptosis, and cell cycle progression in different NB cell lines...This study provides strong evidence for elucidating CXCR2-targeted therapies as an attractive treatment option for NB. These findings support the development of CXCR2-targeted therapies for high-risk NB.

The effects of mogamulizumab and chemical antagonists of C-C/C-X-C chemokine receptors TAK-799, SB225002, and MK-7123 on SCI recovery in rodents are further estimated. Here blockade of CCR5 and CXCR1/2 chemokine receptors is shown beneficial for amelioration of acute SCI, whereas anti-CCR4 antibody mogamulizumab readily prevents secondary inflammation in the injured area. Summarizing, the current report claims for a novel combined time-resolved therapeutic modality in SCI treatment, which supports feasibility and motivates off-label clinical evaluation in appropriate cohorts.

Therapeutic intervention using the CXCL8-CXCR1/2 inhibitor reparixin disrupted the CXCL8-PD-L1 axis, reduced PD-L1+ macrophage abundance and enhanced CD8+ T cell cytotoxicity. Notably, combination therapy with PD-L1 blockade demonstrated synergistic efficacy. Collectively, our findings reveal a stromal-immune checkpoint axis orchestrated by CD54⁺ iCAFs and ITGAL⁺ macrophages that underpins immunosuppression in CC, thereby providing a translational rationale for stroma-directed combination therapies that may overcome resistance to current immunotherapies.

Therefore, SCH527123 represents a new drug candidate with potential in the fields of inflammation and cancer. Although challenges remain in translating preclinical findings into clinical benefits, ongoing research and development efforts on using SCH527123 hold promise for improving the survival and quality of life of patients with these devastating diseases.

Our findings reveal that NETs contribute to chemoresistance in PDAC and that IL-8-mediated chemoNETosis plays a pivotal role in this process. Inhibition of CXCR1/2-mediated NET formation enhances the efficacy of GEM. This approach may represent a promising therapeutic strategy for overcoming chemoresistance in PDAC. These results support further clinical investigation of anti-NETs therapies.