Everolimus affects vasculogenic mimicry in renal carcinoma resistant to sunitinib.
Everolimus affects vasculogenic mimicry in renal carcinoma resistant to sunitinib.
复制标题
DOI：
10.18632/oncotarget.9542
复制
发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
de Gramont A
中科院分区：
文献类型：
--
作者：
Serova M;Tijeras-Raballand A;Dos Santos C;Martinet M;Neuzillet C;Lopez A;Mitchell DC;Bryan BA;Gapihan G;Janin A;Bousquet G;Riveiro ME;Bieche I;Faivre S;Raymond E;de Gramont A
血管生成是肾透明细胞癌发生的标志。抗血管生成治疗已经成功地改善了疾病的预后；然而，大多数接受抗血管生成药物治疗的患者最终都会进步。在这项研究中，我们报道了透明细胞肾癌与血管生成拟态有关，在小鼠和人类中，肿瘤细胞在肿瘤血管附近表达内皮标记。我们发现，血管生成拟态被舒尼替尼有效地靶向，但最终在体外和体内都与肿瘤耐药性和更具侵袭性的表型有关。在小鼠身上重新挑战这些耐药肿瘤，我们发现与索拉非尼和阿西替尼相比，伊波利莫二线治疗特别影响血管生成拟态和肿瘤细胞分化。最后，我们的结果强调了在舒尼替尼的反应和进展过程中肿瘤细胞和微环境水平的表型和基因变化，以及随后二线治疗给当前的肾癌治疗范例带来的改进。
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.
登录
查看更多内容
影响因子：
3
作者：
Motzer, Robert J.;Hutson, Thomas E.;Hudes, Gary R.;Figlin, Robert A.;Martini, Jean-Francois;English, Patricia A.;Huang, Xin;Valota, Olga;Williams, J. Andrew
通讯作者：
Williams, J. Andrew
影响因子：
6.6
作者：
Choueiri, Toni K.;Vaziri, Susan A. J.;Ganapathi, Ram
通讯作者：
Ganapathi, Ram
影响因子：
5.7
作者：
Makhov PB;Golovine K;Kutikov A;Teper E;Canter DJ;Simhan J;Uzzo RG;Kolenko VM
通讯作者：
Kolenko VM
影响因子：
25.7
作者：
Marijon, Helene;Dokmak, Safi;Faivre, Sandrine
通讯作者：
Faivre, Sandrine
影响因子：
50.3
作者：
Casanovas, O;Hicklin, DJ;Hanahan, D
通讯作者：
Hanahan, D