Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis.
Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis.
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DOI：
10.1016/j.ccr.2009.01.021
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发表时间：
2009-03-03
期刊：
影响因子：
50.3
通讯作者：
Kerbel RS
中科院分区：
文献类型：
--
作者：
Ebos JM;Lee CR;Cruz-Munoz W;Bjarnason GA;Christensen JG;Kerbel RS
在此，我们报告，VEGFR/PDGFR 激酶抑制剂舒尼替尼/SU11248 可以加速转移性肿瘤的生长，并降低在各种转移试验中接受短期治疗的小鼠的总体生存率，包括静脉注射肿瘤细胞后或切除原发性原位生长的肿瘤后。在静脉内植入肿瘤细胞之前接受舒尼替尼的小鼠中也观察到转移加速，这表明多个器官可能存在“转移调理”。其他 VEGF 受体酪氨酸激酶抑制剂的类似发现表明此类药物具有特定类别的作用。重要的是，这些转移加速的观察结果与当相同的人类乳腺癌细胞以及小鼠或人类黑色素瘤细胞作为原发肿瘤原位生长并接受相同的舒尼替尼治疗时所获得的明显抗肿瘤益处形成对比。
Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible “metastatic conditioning” in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments.