Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer
Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer
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DOI：
10.1093/annonc/mdn710
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发表时间：
2009-05-01
影响因子：
50.5
通讯作者：
O'Donovan, N.
中科院分区：
文献类型：
--
作者：
Corkery, B.;Crown, J.;O'Donovan, N.
背景：目前尚无经证实的靶向治疗可用于治疗三阴性乳腺癌（TNBC）。表皮生长因子受体（EGFR）在TNBC中经常过表达。我们研究了EGFR拮抗剂单独的活性，并与化疗相结合，在TNBC细胞line.Materials和方法：EGFR和磷酸化EGFR测定酶联免疫吸附试验。评估了EGFR抑制剂单独使用和与化疗联合使用的敏感性。吉非替尼对EGFR信号传导和细胞周期的影响也examined.Results：EGFR过表达的TNBC相比，人表皮生长因子受体2（HER-2）阳性细胞系。在TNBC细胞中检测到EGFR的磷酸化响应于表皮生长因子刺激，并被吉非替尼治疗阻断。然而，TNBC细胞系对EGFR抑制的敏感性低于HER-2阳性细胞系。对吉非替尼的反应与丝裂原活化蛋白激酶（MAPK）和Akt的磷酸化减少以及G（1）阻滞的诱导有关。吉非替尼增强了TNBC细胞对卡铂和多西他赛的反应，并且吉非替尼、卡铂和多西他赛的三重组合具有协同作用。结论：虽然TNBC细胞对EGFR抑制的敏感性低于HER-2阳性细胞系，但吉非替尼增强了对化疗的反应。吉非替尼联合卡铂和多西他赛值得在TNBC中进行进一步研究。
Background: No proven targeted therapy is currently available for the treatment of triple-negative breast cancer (TNBC). Epidermal growth factor receptor (EGFR) is frequently overexpressed in TNBC. We studied the activity of EGFR antagonists alone, and in combination with chemotherapy, in TNBC cell lines.Materials and methods: EGFR and phosphorylated EGFR were measured by enzyme-linked immunosorbent assay. Sensitivity to EGFR inhibitors alone and in combination with chemotherapy was assessed. Effects of gefitinib on EGFR signalling and cell cycle were also examined.Results: EGFR was overexpressed in the TNBC compared with the human epidermal growth factor receptor 2 (HER-2)-positive cell lines. Phosphorylation of EGFR was detected in the TNBC cells in response to epidermal growth factor stimulation and was blocked by gefitinib treatment. However, the TNBC cell lines were less sensitive to EGFR inhibition than the HER-2-positive cell lines. Response to gefitinib was associated with reduced phosphorylation of both mitogen activated protein kinase (MAPK) and Akt and induction of G(1) arrest. Gefitinib enhanced response to both carboplatin and docetaxel in the TNBC cells, and the triple combination of gefitinib, carboplatin and docetaxel was synergistic.Conclusions: Although the TNBC cells are less sensitive to EGFR inhibition than the HER-2-positive cell lines, gefitinib enhanced response to chemotherapy. Gefitinib combined with carboplatin and docetaxel warrants further investigation in TNBC.