The endothelial cell CXCR2 receptor pathway may be a novel target for anti-angiogenesis therapy. AZD5069 may have clinical utility as a novel angiogenesis blocker in human disease.

P1/2, N=120, Not yet recruiting, National Cancer Institute (NCI)

P1, N=60, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting

Pharmacological inhibition of CCR5, CXCR2, and IL1R1 with maraviroc, navarixin, and anakinra, respectively, disrupted this cytokine axis, suppressing metastatic colonization in vivo. Our findings reveal that blocking cytokine receptor signaling disrupts the pro-metastatic crosstalk between macrophages and TNBC cells, offering a clinically actionable strategy to restrain metastasis and overcome therapy resistance in TNBC.

By controlling the translation of SASP factors, the mechanistic Target of Rapamycin (mTOR) is a central regulator of senescence...Here, we demonstrate the possibility to counteract both the autocrine senescence in LAM/TSC cells and senescence induced on PLFs by inhibiting CXCR2, an IL-8 receptor that controls the senescent response to IL-8 stimuli, through the small molecule SB225002...Interestingly, IL-8 is enriched in the LAM/TSC sEVs samples compared to PLFs. Taken together, our results indicate the therapeutic potential to interfere with senescence spreading in lung microenvironment and suggest the employment of molecules targeting senescence as a worthy pharmacological approach for LAM.

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

P2, N=53, Recruiting, Syntrix Biosystems, Inc. | Trial primary completion date: Jun 2026 --> Jun 2027

P2, N=10, Recruiting, Icahn School of Medicine at Mount Sinai | N=26 --> 10 | Trial primary completion date: Dec 2026 --> Dec 2027

P1, N=60, Not yet recruiting, Eli Lilly and Company

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.