STTT：王洁团队发现肺癌脑转移治疗新靶点——LCN2

Core Viewpoint - The study highlights the critical role of LCN2 in driving brain metastasis in lung cancer and proposes it as a potential therapeutic target for brain metastatic lung cancer [2][7]. Group 1: Research Findings - The research team demonstrated that the upregulation of LCN2 expression in tumor cells promotes brain metastasis by coordinating interactions between metastatic tumor cells, astrocytes, and macrophages [4]. - Brain metastatic tumor cells secrete LCN2, which binds to SLC22A17 on astrocytes, activating the JAK2/STAT3 signaling pathway, leading to astrocyte activation and chemokine secretion, thereby promoting macrophage recruitment [4]. - Macrophages secrete interleukin-1β (IL-1β), which further upregulates LCN2 expression in tumor cells [4]. Group 2: Therapeutic Implications - Preventive use of the interleukin-1 receptor antagonist Anakinra can inhibit the formation of brain metastases, while therapeutic use alone is ineffective [5]. - The use of the STAT3 inhibitor SH4-54, either alone or in combination with Anakinra, significantly inhibits the growth of brain metastases [5]. - Tumor-secreted LCN2 can also bind to SLC22A17 on tumor cells, activating the JAK2/STAT3 signaling pathway, which promotes the expression and release of VEGF-A, enhancing tumor angiogenesis [5].