Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins.

@article{Guix2008AcquiredRT,
  title={Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins.},
  author={Marta Guix and Anthony C Faber and Shizhen Emily Wang and Mar{\'i}a Graciela Olivares and Youngchul Song and Sherman Qu and Cammie Rinehart and Brenda Seidel and Douglas Yee and Carlos L. Arteaga and Jeffrey A. Engelman},
  journal={The Journal of clinical investigation},
  year={2008},
  volume={118 7},
  pages={2609-19}
}
Although some cancers are initially sensitive to EGFR tyrosine kinase inhibitors (TKIs), resistance invariably develops. We investigated mechanisms of acquired resistance to the EGFR TKI gefitinib by generating gefitinib-resistant (GR) A431 squamous cancer cells. In GR cells, gefitinib reduced phosphorylation of EGFR, ErbB-3, and Erk but not Akt. These cells also showed hyperphosphorylation of the IGFI receptor (IGFIR) and constitutive association of IRS-1 with PI3K. Inhibition of IGFIR… CONTINUE READING
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