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

Higher CSF CXCL1 levels before pCSI are linked to worse treatment response and increased LM growth in patients with leptomeningeal metastasis.

• Why it matters: Understanding molecular factors that influence pCSI resistance is crucial because LM has a fatal prognosis and variable treatment outcomes, highlighting the need for targeted interventions.
• What they did: Proteomic analysis of CSF from LM patients identified CXCL1 as associated with disease progression; mouse models showed that cancer cell-derived CXCL1 promotes LM growth via Cxcr2, with higher Cxcr2 expression correlating with poorer survival.
• The result: Blocking Cxcl1-Cxcr2 signaling reduced LM growth and increased sensitivity to radiation therapy in preclinical models, suggesting this pathway as a potential target to improve pCSI efficacy and patient outcomes.