her2 oncogenic function escapes egfr tyrosine kinase inhibitors via activation of alternative her receptors in breast cancer cellsher2致癌功能逃表皮生长因子受体酪氨酸激酶抑制剂通过激活受体在乳腺癌细胞的替代她.pdfVIP

HER2 Oncogenic Function Escapes EGFR Tyrosine Kinase Inhibitors via Activation of Alternative HER Receptors in Breast Cancer Cells 1,2 ´ 1 4 3 2,5 ´ Anthony Kong , Veronique Calleja , Pierre Leboucher , Adrian Harris , Peter J. Parker , Banafshe Larijani1* 1 Cell Biophysics Laboratory, Lincoln’s Inn Fields laboratories, London Research Institute, Cancer Research UK, London, United Kingdom, 2 Protein Phosphorylation Laboratory, Lincoln’s Inn Fields laboratories, London Research Institute, Cancer Research UK, London, United Kingdom, 3 Weatherall Institute of Molecular Medicine (IMM), Cancer Research UK, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom, 4 Laboratoire de Physiologie de la Perception et de l’Action, College de France, Paris, France, 5 Division of Cancer Studies, King’s College School of Medicine, Guy’s Hospital, London, United Kingdom Abstract Background: The response rate to EGFR tyrosine kinase inhibitors (TKIs) may be poor and unpredictable in cancer patients with EGFR expression itself being an inadequate response indicator. There is limited understanding of the mechanisms underlying this resistance. Furthermore, although TKIs suppress the growth of HER2-overexpressing breast tumor cells, they do not fully inhibit HER2 oncogenic function at physiological doses. Methodology and Principal Findings: Here we have provided a molecular mechanism of how HER2 oncogenic function ¨ escapes TKIs’ inhibition via alternative HER receptor activation as a result of autocrine ligand release. Using both Forster Res