This study systematically delineates a novel panel of early-detection biomarkers for CRC and identifies SB-225002 as a repurposed candidate therapeutic agent. The integrative strategy combining multi-cohort transcriptomic analysis, drug-repositioning platforms, molecular docking, and experimental validation offers a feasible framework for discovering clinically actionable biomarkers and small-molecule therapies for CRC.

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

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