Lapatinib in combination with radiation diminishes tumor regrowth in HER2+ and basal-like/EGFR+ breast tumor xenografts.
Lapatinib in combination with radiation diminishes tumor regrowth in HER2+ and basal-like/EGFR+ breast tumor xenografts.
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DOI：
10.1016/j.ijrobp.2009.12.063
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发表时间：
2010-06-01
影响因子：
7
通讯作者：
Shields, Janiel M.
中科院分区：
文献类型：
--
作者：
Sambade, Maria J.;Kimple, Randall J.;Camp, J. Terese;Peters, Eldon;Livasy, Chad A.;Sartor, Carolyn I.;Shields, Janiel M.
确定拉帕替尼（一种表皮生长因子受体 (EGFR)/HER2 激酶双重抑制剂）是否可以使 EGFR+ 或 HER2+ 乳腺癌异种移植物放射增敏。携带 basal-like/EGFR+ SUM149 和 HER2+ SUM225 乳腺癌细胞异种移植物的小鼠接受拉帕替尼和分段放射治疗，通过免疫组织化学检测肿瘤生长抑制与 ERK1 和 AKT 激活的变化相关。基底样/EGFR+ SUM149乳腺癌肿瘤对单独拉帕替尼治疗完全耐药，但拉帕替尼加放疗后生长严重受损，在研究期间表现出平均增强率2.75和平均肿瘤产物分数比2.20。相比之下，HER2+ SUM225 乳腺癌肿瘤对单独拉帕替尼治疗高度敏感，并且在拉帕替尼加放疗的研究期间产生相对较低的平均增强率 1.25。联合治疗在 HER2+ SUM225 模型中的持久肿瘤控制比单独拉帕替尼或放疗更有效。免疫组织化学分析表明，拉帕替尼的放射增敏作用与 EGFR+ SUM149 模型中的 ERK1/2 抑制相关，以及 HER2+ SUM225 模型中的 AKT 抑制相关。我们的数据表明，拉帕替尼联合分段放疗可能对 EGFR+ 和 HER2+ 乳腺癌有效，并且抑制 ERK1/2 和 AKT 下游信号传导分别与 EGFR+ 和 HER2+ 细胞的敏化相关。
To determine whether lapatinib, a dual epidermal growth factor receptor (EGFR)/HER2 kinase inhibitor, can radiosensitize EGFR+ or HER2+ breast cancer xenografts. Mice bearing xenografts of basal-like/EGFR+ SUM149 and HER2+ SUM225 breast cancer cells were treated with lapatinib and fractionated radiotherapy and tumor growth inhibition correlated with alterations in ERK1 and AKT activation by immunohistochemistry. Basal-like/EGFR+ SUM149 breast cancer tumors were completely resistant to treatment with lapatinib alone but highly growth impaired with lapatinib plus radiotherapy, exhibiting an enhancement ratio average of 2.75 and a fractional tumor product ratio average of 2.20 during the study period. In contrast, HER2+ SUM225 breast cancer tumors were highly responsive to treatment with lapatinib alone and yielded a relatively lower enhancement ratio average of 1.25 during the study period with lapatinib plus radiotherapy. Durable tumor control in the HER2+ SUM225 model was more effective with the combination treatment than either lapatinib or radiotherapy alone. Immunohistochemical analyses demonstrated that radiosensitization by lapatinib correlated with ERK1/2 inhibition in the EGFR+ SUM149 model and with AKT inhibition in the HER2+ SUM225 model. Our data suggest that lapatinib combined with fractionated radiotherapy may be useful against EGFR+ and HER2+ breast cancers and that inhibition of downstream signaling to ERK1/2 and AKT correlates with sensitization in EGFR+ and HER2+ cells, respectively.
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拉帕替尼对转移性乳腺癌细胞生长到大脑的影响。
影响因子：
10.3
作者：
Gril, Brunilde;Palmieri, Diane;Bronder, Julie L.;Herring, Jeanne M.;Vega-Valle, Eleazar;Feigenbaum, Lionel;Liewehr, David J.;Steinberg, Seth M.;Merino, Maria J.;Rubin, Stephen D.;Steeg, Patricia S.
通讯作者：
Steeg, Patricia S.
DOI：
10.1016/j.radonc.2009.09.006
发表时间：
2009-12
期刊：
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
影响因子：
--
作者：
Sambade MJ;Camp JT;Kimple RJ;Sartor CI;Shields JM
通讯作者：
Shields JM
影响因子：
50.5
作者：
Blackwell, K. L.;Pegram, M. D.;Burstein, H. J.
通讯作者：
Burstein, H. J.
影响因子：
3.8
作者：
Cameron, David;Casey, Michelle;Geyer, Charles E.
通讯作者：
Geyer, Charles E.
影响因子：
3
作者：
Rixe, Olivier;Franco, Sandra X.;Rugo, Hope S.
通讯作者：
Rugo, Hope S.