Cancer Therapy: Preclinical Transient PI3K Inhibition Induces Apoptosis and Overcomes HGF-Mediated Resistance to EGFR-TKIs in EGFR Mutant Lung Cancer

نویسندگان

  • Ivan S. Donev
  • Wei Wang
  • Tadaaki Yamada
  • Qi Li
  • Shinji Takeuchi
  • Kunio Matsumoto
  • Takao Yamori
  • Yasuhiko Nishioka
  • Saburo Sone
  • Seiji Yano
چکیده

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib, show favorable response to EGFR mutant lung cancer. However, the responders acquire resistance almost without exception. We recently reported that hepatocyte growth factor (HGF) induces EGFR-TKI resistance by activatingMET that restores downstreammitogen activated protein kinase (MAPK)/ extracellular signal regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K)/Akt signaling. The purpose of this study was to determine whether inhibition of PI3K, a downstream molecule of both EGFR and MET, could overcome HGF-mediated EGFR-TKI resistance in EGFRmutant lung cancer cells PC-9 and

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Transient PI3K inhibition induces apoptosis and overcomes HGF-mediated resistance to EGFR-TKIs in EGFR mutant lung cancer.

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تاریخ انتشار 2011