P2, N=32, Not yet recruiting, University of Washington | Initiation date: Mar 2026 --> Jun 2026

Low UFL1 expression synergized with anti-PD-1 therapy to prolong survival in orthotopic and spontaneous HCC models, whereas pharmacologic inhibition of CXCL8-CXCR1/2 signaling using SX-682 recapitulated these effects. Clinically, patients who responded to immunotherapy exhibited reduced UFL1, PRMT5 and CXCL8 expression; decreased neutrophil infiltration; elevated CD8+ T-cell activity; and lower serum CXCL8 levels. These findings reveal a UFL1-PRMT5-NF-κB p65-CXCL8 axis that governs neutrophil-driven immunosuppression and identify CXCL8 as both a predictive biomarker and therapeutic target to optimize immunotherapy in patients with HCC.

Pharmacological inhibition of the CXCR1/2 axis with reparixin effectively blocked OCM-mediated induction of both NFIX and FRY, suggesting that chemokine signaling initiates this pro-invasive loop. Collectively, these findings suggest that FRY is a macrophage-driven mediator of invasion and underscore its potential relevance in ovarian cancer.

Further treatment with CXCL5 ligand significantly induced neuritogenesis, while the neurite outgrowth was abrogated when cotreated with CXCR2 (receptor for CXCL5) inhibitor SCH527123...NR4A2 knockdown in UMSCC1 cells impaired tumor formation in vivo, and the xenograft tissues exhibited significant downregulation of CXCL5, providing direct in vivo evidence for the NR4A2-CXCL5 axis in tumor progression. NR4A2 is a key driver of CXCL5-mediated PNI and the NR4A2/CXCL5/CXCR2 signaling axis is a potential therapeutic target in HNSCC and PDAC.

P1/2, N=51, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jul 2026 | Trial primary completion date: Jan 2026 --> Jul 2026

We treated parental and GemR cell lines with gemcitabine in combination with a CXCR2 antagonist, Navarixin. In conclusion, these findings highlight the critical role of the CXCR2 axis in PDAC therapy resistance. Targeting CXCR2 enhances gemcitabine efficacy, offering a potential therapeutic strategy to overcome resistance in PDAC.

P2, N=32, Not yet recruiting, University of Washington

P1, N=77, Active, not recruiting, Syntrix Biosystems, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Aug 2026

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

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.