CXCL1-CXCR2 signaling mediates cancer cell growth and response to radiation therapy in leptomeningeal metastasis.

CXCL1-CXCR2 signaling drives leptomeningeal metastasis growth and predicts poor response to radiation therapy, with higher levels linked to worse outcomes.

• Why it matters: Leptomeningeal metastasis is a deadly complication with limited treatment options, and understanding molecular mechanisms of therapy resistance is crucial for improving patient survival.
• What they did: Proteomic analysis of cerebrospinal fluid from LM patients identified CXCL1 as a key factor; mouse models showed that disrupting CXCL1 in cancer cells impairs tumor growth, and blocking CXCR2 reduces LM progression.
• The result: Targeting the CXCL1-CXCR2 pathway slowed LM growth and increased sensitivity to radiation in preclinical models, suggesting this axis as a promising therapeutic target to enhance treatment response.