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首页> 外文期刊>Cancer Cell >Postsurgical Adjuvant Tumor Therapy by Combining Anti-Angiopoietin-2 and Metronomic Chemotherapy Limits Metastatic Growth
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Postsurgical Adjuvant Tumor Therapy by Combining Anti-Angiopoietin-2 and Metronomic Chemotherapy Limits Metastatic Growth

机译：结合抗血管生成素2和节律性化学疗法的手术后辅助肿瘤治疗限制了转移性生长。

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摘要

Antiangiogenic tumor therapy has failed in the adjuvant setting. Here we show that inhibition of the Tie2 ligandangiopoietin-2 (Ang2) effectively blocks metastatic growth in preclinical mouse models of postsurgical adjuvant therapy. Ang2 antibody treatment combines well with low-dose metronomic chemotherapy (LDMC) in settings in which maximum-dose chemotherapy does not prove effective. Mechanistically, Ang2 blockade could be linked to quenching the inflammatory and angiogenic response of endothelial cells (ECs) in the metastatic niche. Reduced EC adhesion molecule and chemokine expression inhibits the recruitment of tumor-promoting CCR2+Tie2- metastasis-associated macrophages. Moreover, LDMC contributes to therapeutic efficacy by inhibiting the recruitment of protumorigenic bone marrow-derived myeloid cells. Collectively, these data provide a rationale for mechanism-guided adjuvant tumor therapies.
机译：抗血管生成肿瘤治疗在辅助治疗中失败。在这里，我们显示抑制Tie2配体血管生成素2（Ang2）有效地阻止了术后辅助治疗的临床前小鼠模型中的转移性生长。在大剂量化疗无效的情况下，Ang2抗体治疗可与低剂量节律化疗（LDMC）完美结合。从机制上讲，Ang2阻断作用可能与猝灭转移小生境中的内皮细胞（EC）的炎症反应和血管生成反应有关。 EC粘附分子和趋化因子表达的降低抑制了促进肿瘤的CCR2 + Tie2-转移相关巨噬细胞的募集。此外，LDMC通过抑制肿瘤原性骨髓来源的骨髓细胞的募集而有助于治疗效果。总体而言，这些数据为机制指导的辅助肿瘤治疗提供了理论依据。

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