表皮生长因子受体（EGFR）、雷帕霉素靶蛋白（mTOR）和磷脂酰肌醇-3激酶（PI3K）抑制剂在同基因乳腺癌细胞系模型中的活性
Activity of EGFR, mTOR and PI3K inhibitors in an isogenic breast cell line model.
作者信息
Glaysher Sharon, Bolton Louise M, Johnson Penny, Torrance Christopher, Cree Ian A
机构信息
Department of Pathology, University Hospitals Coventry and Warwickshire, Coventry, UK.
出版信息
BMC Res Notes. 2014 Jun 25;7:397. doi: 10.1186/1756-0500-7-397.
BACKGROUND
The epidermal growth factor receptor family is expressed in breast cancer, and agents targeting this pathway have single agent effects (e.g. traztuzumab). Development of resistance may be due to the presence of alternative pathways, particularly activation of the PI3K/Akt/MTOR pathway. We have therefore examined the effect of inhibitors of this pathway (ZSTK474 and sirolimus) in combination with the epidermal growth factor (EGFR) inhibitors erlotinib and gefitinib in breast MCF10a isogenic cell lines with EGFR, BRAF, AKT, and PI3K mutations.
RESULTS
PI3K mutation conferred increased activity of EGFR inhibitors against MCF10a cells in comparison with the parental cell line and other mutations studied. Combination of EGFR inhibitors with either the PI3K inhibitor ZSTK474 or the MTOR inhibitor sirolimus showed increased activity.
CONCLUSIONS
These results are encouraging for the use of combinations targeting the PI3K and EGFR pathway simultaneously.
背景
表皮生长因子受体家族在乳腺癌中表达，靶向该通路的药物具有单药效应（如曲妥珠单抗）。耐药性的产生可能归因于替代通路的存在，特别是PI3K/Akt/MTOR通路的激活。因此，我们研究了该通路抑制剂（ZSTK474和西罗莫司）与表皮生长因子（EGFR）抑制剂厄洛替尼和吉非替尼联合使用对具有EGFR、BRAF、AKT和PI3K突变的乳腺癌MCF10a同基因细胞系的影响。
结果
与亲本细胞系及其他研究的突变相比，PI3K突变使EGFR抑制剂对MCF10a细胞的活性增加。EGFR抑制剂与PI3K抑制剂ZSTK474或MTOR抑制剂西罗莫司联合使用显示出活性增加。
结论
这些结果对于同时靶向PI3K和EGFR通路的联合用药是令人鼓舞的。
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