• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer Cell >Inhibition of PI3K/mTOR Leads to Adaptive Resistance in Matrix-Attached Cancer Cells
【24h】

Inhibition of PI3K/mTOR Leads to Adaptive Resistance in Matrix-Attached Cancer Cells

机译：PI3K / mTOR的抑制导致基质附着癌细胞的适应性耐药

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The PI3K/mTOR-pathway is the most commonly dysregulated pathway in epithelial cancers and represents an important target for cancer therapeutics. Here, we show that dual inhibition of PI3K/mTOR in ovarian cancer-spheroids leads to death of inner matrix-deprived cells, whereas matrix-attached cells are resistant. This matrix-associated resistance is mediated by drug-induced upregulation of cellular survival programs that involve both FOXO-regulated transcription and cap-independent translation. Inhibition of any one of several upregulated proteins, including Bcl-2, EGFR, or IGF1R, abrogates resistance to PI3K/mTOR inhibition. These results demonstrate that acute adaptive responses to PI3K/mTOR inhibition in matrix-attached cells resemble well-conserved stress responses to nutrient and growth factor deprivation. Bypass of thisresistance mechanism through rational design of drug combinations could significantly enhance PI3K-targeted drug efficacy.
机译：PI3K / mTOR途径是上皮癌中最常见的失调途径，并且代表癌症治疗的重要靶标。在这里，我们表明卵巢癌椭球体中PI3K / mTOR的双重抑制导致内部基质被剥夺的细胞死亡，而基质附着的细胞则具有抗性。这种与基质相关的抗性是由药物诱导的细胞存活程序的上调介导的，该程序涉及FOXO调节的转录和独立于帽的翻译。抑制几种上调的蛋白质中的任何一种，包括Bcl-2，EGFR或IGF1R，都可以消除对PI3K / mTOR抑制的抗性。这些结果表明，对基质附着细胞中PI3K / mTOR抑制的急性适应性反应类似于对营养和生长因子缺乏的保守保存的应激反应。通过合理设计药物组合来绕开这种抗药性机制可以显着提高针对PI3K的药物疗效。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号