期刊
ONCOTARGET
卷 7, 期 25, 页码 38467-38486出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9542
关键词
everolimus; sunitinib; renal cell carcinoma; angiogenesis; differentiation
资金
- Novartis (REVERST project)
- Foundation Nelia & Amadeo Barleta (FNAB)
- Association d'Aide a la Recherche et a l'Enseignement en Cancerologie (AAREC)
Angiogenesis is hallmark of clear cell renal cell carcinogenesis. Anti-angiogenic therapies have been successful in improving disease outcome; however, most patients treated with anti-angiogenic agents will eventually progress. In this study we report that clear cell renal cell carcinoma was associated with vasculogenic mimicry in both mice and human with tumor cells expressing endothelial markers in the vicinity of tumor vessels. We show that vasculogenic mimicry was efficiently targeted by sunitinib but eventually associated with tumor resistance and a more aggressive phenotype both in vitro and in vivo. Re-challenging these resistant tumors in mice, we showed that second-line treatment with everolimus particularly affected vasculogenic mimicry and tumor cell differentiation compared to sorafenib and axitinib. Finally, our results highlighted the phenotypic and genotypic changes at the tumor cell and microenvironment levels during sunitinib response and progression and the subsequent improvement second-line therapies bring to the current renal cell carcinoma treatment paradigm.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据